Luminal organ sizing devices and methods

ABSTRACT

Luminal organ sizing devices and methods. In a method of the present disclosure, the method includes performing a valve replacement procedure using a valve device positioned within a valve annulus or opening of a luminal organ while a system including a balloon configured for inflation is at least partially introduced into a luminal organ so that the balloon is adjacent to a valve annulus or opening.

RELATED APPLICATIONS

The present application is related to, and claims the priority benefitof, A) U.S. Provisional Patent Application Ser. No. 62/627,525, filedFeb. 7, 2018, and B) U.S. Provisional Patent Application Ser. No.62/613,814, filed Jan. 5, 2018, and is related to, claims the prioritybenefit of, and is a U.S. continuation-in-part patent application of,U.S. patent application Ser. No. 16/011,007, filed Jun. 18, 2018, whichi) is related to, claims the priority benefit of, U.S. ProvisionalPatent Application Ser. No. 62/521,024, filed Jun. 16, 2017, and ii) isrelated to, claims the priority benefit of, and is a U.S.continuation-in-part patent application of, U.S. patent application Ser.No. 15/156,364, filed May 17, 2016, which a) is related to, and claimsthe priority benefit of, Provisional Patent Application Ser. No.62/261,357, filed Dec. 1, 2015, and b) is related to, claims thepriority benefit of, and is a continuation-in-part application of, U.S.patent application Ser. No. 13/850,758, filed Mar. 26, 2013 and issuedas U.S. Pat. No. 9,339,230 on May 17, 2016, which is related to, claimsthe priority benefit of, and is a continuation application of, U.S.patent application Ser. No. 12/706,677, filed Feb. 16, 2010 and issuedas U.S. Pat. No. 8,406,867 on Mar. 26, 2013, which is related to, claimsthe priority benefit of, and is a continuation-in-part application of,U.S. patent application Ser. No. 11/891,981, filed Aug. 14, 2007 andissued as U.S. Pat. No. 8,114,143 on Feb. 14, 2012, which is related to,claims the priority benefit of, and is a divisional application of, U.S.patent application Ser. No. 10/782,149, filed Feb. 19, 2004 and issuedas U.S. Pat. No. 7,454,244 on Nov. 18, 2008, which is related to, andclaims the priority benefit of, U.S. Provisional Patent Application Ser.No. 60/449,266, filed Feb. 21, 2003, U.S. Provisional Patent ApplicationSer. No. 60/493,145, filed Aug. 7, 2003, and U.S. Provisional PatentApplication Ser. No. 60/502,139, filed Sep. 11, 2003. The contents ofeach of these applications and patents are hereby incorporated byreference in their entirety into this disclosure.

BACKGROUND

Coronary heart disease (CHD) is commonly caused by atheroscleroticnarrowing of the coronary arteries and is likely to produce anginapectoris, heart attacks or a combination. CHD caused 466,101 deaths inthe USA in 1997 and is one of the leading causes of death in Americatoday. Approximately, 12 million people alive today have a history ofheart attack, angina pectoris or both. The break down for males andfemales is 49% and 51%, respectively. This year, an estimated 1.1million Americans will have a new or recurrent coronary attack, and morethan 40% of the people experiencing these attacks will die as a result.About 225,000 people a year die of coronary attack without beinghospitalized. These are sudden deaths caused by cardiac arrest, usuallyresulting from ventricular fibrillation. More than 400,000 Americans and800,000 patients world-wide undergo a non-surgical coronary arteryinterventional procedure each year. Although only introduced in the1990s, in some laboratories intra-coronary stents are used in 90% ofthese patients.

Stents increase minimal coronary lumen diameter to a greater degree thanpercutaneous transluminal coronary angioplasty (PTCA) alone according tothe results of two randomized trials using the Palmaz-Schatz stent.These trials compared two initial treatment strategies: stenting aloneand PTCA with “stent backup” if needed. In the STRESS trial, there was asignificant difference in successful angiographic outcome in favor ofstenting (96.1% vs. 89.6%).

Intravascular Ultrasound

Currently intravascular ultrasound is the method of choice to determinethe true diameter of the diseased vessel in order to size the stentcorrectly. The term “vessel,” as used herein, refers generally to anyhollow, tubular, or luminal organ. The tomographic orientation ofultrasound enables visualization of the full 360° circumference of thevessel wall and permits direct measurements of lumen dimensions,including minimal and maximal diameter and cross-sectional area.Information from ultrasound is combined with that obtained byangiography. Because of the latticed characteristics of stents,radiographic contrast material can surround the stent, producing anangiographic appearance of a large lumen, even when the stent struts arenot in full contact with the vessel wall. A large observationalultrasound study after angio-graphically guided stent deploymentrevealed an average residual plaque area of 51% in a comparison ofminimal stent diameter with reference segment diameter, and incompletewall apposition was frequently observed. In this cohort, additionalballoon inflations resulted in a final average residual plaque area of34%, even though the final angiographic percent stenosis was negative(20.7%). These investigators used ultrasound to guide deployment.

However, using intravascular ultrasound as mentioned above requires afirst step of advancement of an ultrasound catheter and then withdrawalof the ultrasound catheter before coronary angioplasty thereby addingadditional time to the stent procedure. Furthermore, it requires anultrasound machine. This adds significant cost and time and more risk tothe procedure.

Aortic Stenosis

Aortic Stenosis (AS) is one of the major reasons for valve replacementsin adult. AS occurs when the aortic valve orifice narrows secondary tovalve degeneration. The aortic valve area is reduced to one fourth ofits normal size before it shows a hemodynamic effect. Because the areaof the normal adult valve orifice is typically 3.0 to 4.0 cm², an area0.75-1.0 cm² is usually not considered severe AS. When stenosis issevere and cardiac output is normal, the mean trans-valvular pressuregradient is generally >50 mmHg. Some patients with severe AS remainasymptomatic, whereas others with only moderate stenosis developsymptoms. Therapeutic decisions, particularly those related tocorrective surgery, are based largely on the presence or absence ofsymptoms.

The natural history of AS in the adult consists of a prolonged latentperiod in which morbidity and mortality are very low. The rate ofprogression of the stenotic lesion has been estimated in a variety ofhemodynamic studies performed largely in patients with moderate AS.Cardiac catheterization and Doppler echocardiographic studies indicatethat some patients exhibit a decrease in valve area of 0.1-0.3 cm² peryear; the average rate of change is 0.12 cm² per year. The systolicpressure gradient across the valve may increase by as much as 10 to 15mmHg per year. However, more than half of the reported patients showedlittle or no progression over a 3-9 year period. Although it appearsthat progression of AS can be more rapid in patients with degenerativecalcific disease than in those with congenital or rheumatic disease, itis not possible to predict the rate of progression in an individualpatient.

Eventually, symptoms of angina, syncope, or heart failure develop aftera long latent period, and the outlook changes dramatically. After onsetof symptoms, average survival is <2-3 years. Thus, the development ofsymptoms identifies a critical point in the natural history of AS.

Many asymptomatic patients with severe AS develop symptoms within a fewyears and require surgery. The incidence of angina, dyspnea, or syncopein asymptomatic patients with Doppler outflow velocities of 4 m/s hasbeen reported to be as high as 38% after 2 years and 79% after 3 years.Therefore, patients with severe AS require careful monitoring fordevelopment of symptoms and progressive disease.

Indications for Cardiac Catheterization

In patients with AS, the indications for cardiac catheterization andangiography are to assess the coronary circulation (to confirm theabsence of coronary artery disease) and to confirm or clarify theclinical diagnosis of AS severity. If echocardiographic data are typicalof severe isolated. AS, coronary angiography may be all that is neededbefore aortic valve replacement (AVR). Complete left- and right-heartcatheterization may be necessary to assess the hemodynamic severity ofAS if there is a discrepancy between clinical and echocardiographic dataor evidence of associated valvular or congenital disease or pulmonaryhypertension.

The pressure gradient across a stenotic valve is related to the valveorifice area and transvalvular flow through Bernoulli's principle. Thus,in the presence of depressed cardiac output, relatively low pressuregradients are frequently obtained in patients with severe AS. On theother hand, during exercise or other high-flow states, systolicgradients can be measured in minimally stenotic valves. For thesereasons, complete assessment of AS requires (1) measurement oftransvalvular flow, (2) determination of the transvalvular pressuregradient, and (3) calculation of the effective valve area. Carefulattention to detail with accurate measurements of pressure and flow isimportant, especially in patients with low cardiac output or a lowtransvalvular pressure gradient.

Problems with Current Aortic Valve Area Measurements

Patients with severe AS and low cardiac output are often present withonly modest transvalvular pressure gradients (i.e., <30 mmHg). Suchpatients can be difficult to distinguish from those with low cardiacoutput and only mild to moderate AS. In both situations, the low-flowstate and low pressure gradient contribute to a calculated effectivevalve area that can meet criteria for severe AS. The standard valve areaformula (simplified Hakki formula which is valve area=cardiacoutput/[pressure gradient]^(1/2)) is less accurate and is known tounderestimate the valve area in low-flow states; under such conditions,it should be interpreted with caution. Although valve resistance is lesssensitive to flow than valve area, resistance calculations have not beenproved to be substantially better than valve area calculations.

In patients with low gradient stenosis and what appears to be moderateto severe AS, it may be useful to determine the transvalvular pressuregradient and calculate valve area and resistance during a baseline stateand again during exercise or pharmacological (i.e., dobutamine infusion)stress. Patients who do not have true, anatomically severe stenosisexhibit an increase in the valve area during an increase in cardiacoutput. In patients with severe AS, these changes may result in acalculated valve area that is higher than the baseline calculation butthat remains in the severe range, whereas in patients without severe AS,the calculated valve area will fall outside the severe range withadministration of dobutamine and indicate that severe AS is not present.

There are many other limitations in estimating aortic valve area inpatients with aortic stenosis using echocardiography and cardiaccatheterization. Accurate measurement of the aortic valve area inpatients with aortic stenosis can be difficult in the setting of lowcardiac output or concomitant aortic or mitral regurgitations.Concomitant aortic regurgitation or low cardiac output can overestimatethe severity of aortic stenosis. Furthermore, because of the dependenceof aortic valve area calculation on cardiac output, any under oroverestimation of cardiac output will cause inaccurate measurement ofvalve area. This is particularly important in patients with tricuspidregurgitation. Falsely measured aortic valve area could causeinappropriate aortic valve surgery in patients who do not need it.

Other Visceral Organs

Visceral organs such as the gastrointestinal tract and the urinary tractserve to transport luminal contents (fluids) from one end of the organto the other end or to an absorption site. The esophagus, for example,transports swallowed material from the pharynx to the stomach. Diseasesmay affect the transport function of the organs by changing the luminalcross-sectional area, the peristalsis generated by muscle, or bychanging the tissue components. For example, strictures in the esophagusand urethra constitute a narrowing of the organ where fibrosis of thewall may occur. Strictures and narrowing can be treated with distension,much like the treatment of plaques in the coronary arteries.

Valve Sizing and Replacement

In addition, percutaneous interventional therapy has been an option forpatients with pulmonic, mitral, and aortic valvular disease for decades.The treatment preferred in selected patients with pulmonic or mitralstenosis is percutaneous valvuloplasty. According to the currentACC/American Heart Association (AHA) guidelines, in patients withcalcific aortic stenosis, balloon aortic valvuloplasty (BAV) has beenused as a bridge to aortic valve replacement.

Hospital mortality for BAV varies from 3.5% to 13.5%, while seriouscomplications appear in at least 25% of the patients. The durability ofBAV is restricted. Consequently, open aortic valve replacement continuesto be the best therapy for aortic stenosis (AS) in patients who areviable candidates for surgery. The most frequent heart valve operationis the aortic valve replacement. In the United States, from 2% to 7% ofindividuals older than 65 years suffer from AS, which will continue toincrease as more people live longer. AS is frequently associated withcomorbid risk factors and previous bypass surgery since it ispersistently progressive and it takes place in elderly patients. Thesurgical therapy for AS patients is useful to improve symptoms andprolong life.

Percutaneous strategies for the treatment of AS began with percutaneousballoon valvuloplasty. Data from the multicenter National Heart, Lung,and Blood Institute (NHLBI) registry, however, showed only a mildprogress in early hemodynamics, a significant incidence of peripheralvascular complications, a 30 day mortality of 7%, and a high incidenceof restenosis within 6 months.

The unsatisfactory BAV results have led to the investigation ofpercutaneous placement of prosthetic aortic valves. Devices to performthe same have been clinically utilized in a small number of cases inhigh-risk patients. Although percutaneous aortic valve insertion hasbeen performed on extremely high-risk patients, considerablepara-valvular leak regurgitation and early mortality discourage theapproach.

One concern with percutaneous or transapical aortic valve replacement isthe sizing of dilatation of the calcific aortic valve prior to deliveryof the stent valve device. The consequences of incorrect sizing of theaortic valve area are periprosthetic leak, calcium embolization, anddifficulties in the insertion of the device and its possible migration.

Ischemic mitral regurgitation (IMR) is a mitral valve insufficiency thatis produced by acute myocardial infarction (AMI) and laterinfarction-induced left ventricular remodeling. Approximately 1.2 to 2.1million patients in the United States suffer IMR, including more than400,000 patients running moderate-to-severe MR. It is estimated thatabout 50-60% of congestive heart failure (CHF) patients suffer from sometype of mitral regurgitation (MR). The valve is structurally normal inthe vast majority of these patients.

In end-stage heart failure patient, the mechanism of MR ismultifactorial and it is related to changes in left ventricular (LV)geometry, with a subsequent displacement of the subvalvular apparatus,annular dilatation, and restrictive leaflet motion, which ends infailure of the leaflet coaptation. Physiologically, IMR in thesepatients will lead to LV overload and decrease of stroke volume.

Numerous investigators support the use of a stringent restrictive ring(which is two sizes smaller than the measured size) in order to obtainbetter leaflet coaptation. This avoids MR recurrence and promotesreverse remodeling. Midterm follow-up (18 months) with this approachshows reverse remodeling in 58% of patients. During direct visualizationin surgery, the sizing of the annulus can be accurately determined andmade appropriate for each patient.

Patients with MR have a considerably diminished survival at 2 years'follow-up versus patients lacking mitral regurgitation. Furthermore, theseverity of mitral regurgitation is directly associated to mortalityrisk. The undersizing of the mitral annulus will lead to acute valuablegeometric changes of the base of the left ventricle, which mightdiminish LV volume and wall stress. When mitral regurgitation is treatedconservatively morbidity and mortality is high.

It seems logical to correct mitral regurgitation in patients withend-stage heart failure (HF) in order to improve prognosis. However, andat the present time, mitral annuloplasty is not routinely performed inthese patients due to significant mortality and elevated recurrencerates. On the other hand, numerous recent investigations havedemonstrated somewhat low operative mortality suggesting improvedlong-term survival after stringent restrictive mitral annuloplasty.

Surgical approaches to MR include mitral valve replacement and repair,with the latest studies supporting early repair in structural MR whenpossible or in patients with ischemic MR and symptomatic HF butmorbidity, mortality, and late recurrent mitral regurgitation limitextensive surgical repair application. Surgical mitral repair could besophisticated and complex, but the majority of repairs currently consistof simple annuloplasty.

Recently, percutaneous approaches to mitral annuloplasty as well aspercutaneous replacement of mitral valve have been shown to reduce MR ofglobal left ventricular dysfunction, acute ischemia, and chronicpost-infarction. A number of devices have been described to remodel orreplace the mitral annulus to decrease annular anteroposterior diameter.

The possibility of balloon sizing of valve annulus prior to committingto a particular size valve is essential. Furthermore, the sizing of thestent valve during delivery will ensure good apposition and preventleak, migration or erosion over the long term.

Thus, a need exists in the art for an alternative to the conventionaldevices and methods for sizing a valve annulus for the subsequentreplacement of mitral valves, for example. A further need exists for areliable, accurate and minimally invasive system or technique of sizinga percutaneous valve and/or a valve annulus and positioning a stentvalve therein.

Furthermore, and by the year 2030, 20% of the American population willbe of age 65 and older, elevating the number of patients at high risk ofsuffering from valvular heart disease to above 70 million. While Aorticstenosis (AS) affects approximately 1.5M Americans, mitral valve (MV)disease accounts for 60% of all valvular diseases, most frequentlymitral regurgitation (MR) which alone affects 7.8 million patients. Ifleft untreated, valvular disease leads to left ventricular (LV)dysfunction/remodeling, reductions in coronary blood flow, heart failure(HF), and eventually death. While transcatheter aortic valve replacement(TAVR) is becoming the new standard (over the surgical approach), themitral valve is most frequently replaced surgically, leaving notreatment options for patients rejected from surgery.

Due mainly to high perioperative mortality risk, about 50% of severemitral stenosis patients never receive surgery, while high risk MRpatients only qualify for Mitral clip. As a result, percutaneouscatheter delivery of a prosthetic mitral valve, called transcathetermitral valve replacement (TMVR), is emerging as a treatment option forsevere MV disease. Compassionate use applications of TAVR valves in MRpatients show promising results for high surgical risk patients in needof a new MV. The FDA has recently approved Edwards Lifesciences Sapien 3for usage as a transcatheter mitral valve for U.S. in both inoperableand high-risk surgical MR patients. While paravalvular leakage used tobe a main concern in patients following TAVR, left ventricular outflowtract (LVOT) obstruction and annular rupture remain the biggest concernsin TMVR. Currently, both multi-detector computed tomography (MDCT),transesophageal echocardiography (TEE) and 3-D printing of the nativevalve based on patient data are used to determine mitral annulus sizeprior to TMVR, but these imaging modalities rely on subjective imageinterpretation for sizing, and are non-dynamic or real time.

Therefore, a new device, method and system that would add no proceduraltime or cost and produces accurate mitral annular sizing measurementsand/or a diagnostic feature of LVOT obstruction during the TMVR implantprocedure would be well received.

BRIEF SUMMARY

In at least one embodiment of a method to size a valve annulus of thepresent disclosure, the method comprises the steps of introducing atleast part of a sizing device into a luminal organ at a valve annulus,the sizing device having a detector and a pressure transducer within aballoon positioned at or near a distal end of the detection device,inflating the balloon until a threshold pressure is detected by thepressure transducer within the balloon, obtaining a first valve annulusmeasurement using the detector, and withdrawing the sizing device fromthe luminal organ. In another embodiment, the method further comprisesthe steps of positioning a stent valve upon the balloon, reintroducingat least part of a sizing device into the luminal organ at the valveannulus, and reinflating the balloon to the first valve annulusmeasurement to place the stent valve within the valve annulus. In yetanother embodiment, the method further comprises the step ofrewithdrawing the sizing device from the luminal organ.

In at least one embodiment of a method to size a valve annulus of thepresent disclosure, the sizing device further comprises a catheterhaving a lumen therethrough and defining a suction/infusion port withinthe catheter within the balloon. In an additional embodiment, the stepof inflating the balloon comprises introducing a fluid into the lumen ofthe catheter, through the suction/infusion port, and into the balloon.In another embodiment, the step of withdrawing the sizing devicecomprises removing fluid from the balloon, through the suction/infusionport, and into the lumen of the catheter, to deflate the balloon. In yetanother embodiment, the detector comprises two detection electrodespositioned in between two excitation electrodes, the excitationelectrodes capable of producing an electric field to facilitate aconductance measurement of a fluid within the balloon. In an additionalembodiment, the step obtaining a first valve annulus measurementcomprises obtaining a balloon cross sectional area using the detector.

In at least one embodiment of a method to size a valve annulus of thepresent disclosure, the step of obtaining a first valve annulusmeasurement comprises measuring a balloon cross-sectional area using thedetector when the threshold pressure is present within the balloon. Inanother embodiment, the balloon cross-sectional area is determined froma conductance measurement of a fluid present within the balloon obtainedby the detector, a known conductivity of the fluid, and a known distancebetween two detection electrodes of the detector.

In at least one embodiment of a method to size a valve annulus of thepresent disclosure, the step of inflating the balloon comprisesinjecting a solution having a known conductivity into the balloon. Inanother embodiment, the step of obtaining a first valve annulusmeasurement comprises measuring a cross-sectional area based in part ofthe conductivity of the fluid and a conductance value obtained using thedetector.

In at least one embodiment of a device to size a valve annulus of thepresent disclosure, the device comprises an elongated body extendingfrom a proximal end to a distal end and having a lumen therethrough, aballoon positioned along the elongated body at or near the distal end, adetector and a pressure transducer positioned along the elongated bodywithin the balloon, and a suction/infusion port defined within theelongated body within the balloon.

In at least one embodiment, the detector comprises a pair of excitationelectrodes located on the elongated body, and a pair of detectionelectrodes located on the elongated body in between the pair ofexcitation electrodes, wherein the detector is capable of obtaining aconductance measurement of a fluid within the balloon. In anotherembodiment, the pair of excitation electrodes are capable of producingan electrical field, and wherein the pair of detection electrodes arecapable of measuring an conductance of the fluid within the balloon. Inan additional embodiment, at least one excitation electrode of the pairof excitation electrodes is/are in communication with a current sourcecapable of supplying electrical current to the at least one excitationelectrode.

In at least one embodiment of a device to size a valve annulus of thepresent disclosure, the device further comprises a data acquisition andprocessing system capable of receiving conductance data from the pair ofdetection electrodes. In an additional embodiment, the data acquisitionand processing system is further capable of calculating a first valveannulus measurement within the balloon based from the conductancemeasurement of the fluid within the balloon obtained by the detector, aknown conductivity of the fluid, and a known distance between the pairof detection electrodes. In another embodiment, the pressure transduceris capable of detecting a pressure within the balloon. In yet anotherembodiment, the suction/infusion port is in communication with the lumenof the elongated body, thereby enabling injection of a solution into thelumen of the elongated body, through the suction/infusion port, and intothe balloon. In various embodiments, the lumen of the elongated body isin communication with a source of a solution to be injected therethroughand through the suction/infusion port into the balloon. In an additionalembodiment, when a fluid is injected through the lumen of the elongatedbody into the balloon, the detector is capable of obtaining a fluidconductance measurement within the balloon, wherein the fluidconductance measurement is useful to determine balloon cross-sectionalarea.

In at least one embodiment of a system to size a valve annulus of thepresent disclosure, the system comprises a device comprising anelongated body extending from a proximal end to a distal end and havinga lumen therethrough, a balloon positioned along the elongated body ator near the distal end, a detector and a pressure transducer positionedalong the elongated body within the balloon, and a suction/infusion portdefined within the elongated body within the balloon, the system alsocomprising a current source coupled to the detector and the pressuretransducer, and a data acquisition and processing system capable ofreceiving conductance data from the detector and calculating a ballooncross-sectional area based upon a detected conductance of a fluid withinthe balloon from the detector, a known conductivity of the fluid, and aknown distance between two detection electrodes of the detector.

In at least one embodiment of a method of the present disclosure, themethod comprises the steps of introducing at least part of a firstdevice into a luminal organ at an aperture or opening of the luminalorgan, the first device having a balloon positioned thereon; inflatingthe balloon at the aperture or opening of the luminal organ until apoint of apposition is achieved; and obtaining a first aperture oropening measurement based upon the point of apposition. In at least oneembodiment of a method of the present disclosure, the first device isconfigured as a catheter having a lumen therethrough and defining asuction/infusion port so that the lumen is in communication with theballoon, and wherein the step of inflating is performed by introducing afluid through the lumen, through the suction/infusion port, and into theballoon.

In at least one embodiment of a method of the present disclosure, thefirst device further comprises at least one electrode positioned withinthe balloon, and the step of obtaining the first aperture or openingmeasurement is performed by obtaining a size measurement within theballoon using the electrode. In at least one embodiment of a method ofthe present disclosure, conductance data is obtained at various stagesof balloon inflation during the inflating step. In at least oneembodiment of a method of the present disclosure, the method furthercomprises the step of operating an ablation contact positioned upon orwithin a surface of the balloon while the balloon is in contact with theluminal organ to ablate the luminal organ. In at least one embodiment ofa method of the present disclosure, the luminal organ comprises a renalartery, and wherein the method is performed to treat hypertension.

In at least one embodiment of a method of the present disclosure, themethod further comprises the step of determining various sizemeasurements of the balloon corresponding to the conductance dataobtained at the various stages of balloon inflation. In at least oneembodiment of a method of the present disclosure, the method furthercomprises the step of determining compliance of the luminal organ at theopening or aperture based upon the various size measurements. In atleast one embodiment of a method of the present disclosure, the openingor aperture is a septum of a heart, and wherein the determining step isperformed to determine compliance of the septum of the heart. In atleast one embodiment of a method of the present disclosure, the methodfurther comprises the step of treating an intraseptal ventricular defectbased upon the determined compliance of the luminal organ.

In at least one embodiment of a method of the present disclosure, themethod comprises the steps of introducing at least part of a firstdevice into a luminal organ so that a balloon of the first device ispositioned at an aperture or opening of the luminal organ; inflating theballoon at the aperture or opening and obtaining conductance data withinthe balloon at various stages of balloon inflation using a detectorpositioned within the balloon; determining various size measurements ofthe balloon corresponding to the conductance data obtained at thevarious stages of balloon inflation; and determining compliance of theluminal organ at the aperture or opening based upon the various sizemeasurements. In at least one embodiment of a method of the presentdisclosure, the step of inflating is performed to inflate the balloon sothat the balloon contacts the luminal organ at the aperture or openingand to obtain conductance data at various stages of balloon prior to theballoon contacting the luminal organ at the aperture or opening andafter the balloon contacts the luminal organ at the aperture or opening.

In at least one embodiment of a method of the present disclosure,compliance of the luminal organ is determined as being rigid orrelatively rigid based upon at least some of the various sizemeasurements corresponding to conductance data obtained after theballoon contacts the luminal organ at the aperture or opening beingconsistent with one another.

In at least one embodiment of a method of the present disclosure,compliance of the luminal organ is determined as being compliant orrelatively compliant based upon an increase in the various sizemeasurements corresponding to conductance data obtained after theballoon contacts the luminal organ at the aperture or opening beingconsistent with one another. In at least one embodiment of a method ofthe present disclosure, compliance of the luminal organ is determined asbeing rigid or relatively right based upon a lack of change in thevarious size measurements corresponding to conductance data obtainedafter the balloon contacts the luminal organ at the aperture or opening.

In at least one embodiment of a method of the present disclosure, themethod further comprises the step of operating an ablation contactpositioned upon or within a surface of the balloon while the balloon isin contact with the luminal organ to ablate the luminal organ. In atleast one embodiment of a method of the present disclosure, the luminalorgan comprises a renal artery, and wherein the method is performed totreat hypertension.

In at least one embodiment of a method of the present disclosure, themethod comprises the steps of introducing at least part of a firstdevice into a luminal organ so that a balloon of the first device ispositioned at an aperture or opening of the luminal organ; firstinflating the balloon at the aperture or opening and obtaining firstconductance data within the balloon at various stages of ballooninflation until the balloon contacts the luminal organ at the apertureor opening; second inflating the balloon at the aperture or opening andobtaining second conductance data within the balloon at various stagesof balloon inflation after the balloon contacts the luminal organ at theaperture or opening; determining various size measurements of theballoon corresponding to the second conductance data; and determiningcompliance of the luminal organ at the aperture or opening based uponthe various size measurements. In at least one embodiment of a method ofthe present disclosure, compliance of the luminal organ is determined asbeing compliant or relatively compliant based upon an increase in thevarious size measurements corresponding to the second conductance data.In at least one embodiment of a method of the present disclosure,compliance of the luminal organ is determined as being rigid orrelatively right based upon a lack of change in the various sizemeasurements corresponding to the second conductance data.

In at least one embodiment of a method of the present disclosure, themethod comprises the steps of introducing at least part of a firstdevice into a luminal organ at an aperture or opening of the luminalorgan at an atrial appendage (referring to the opening of the atrialappendage itself), the first device having a balloon positioned thereon;inflating the balloon at the aperture or opening until a point ofapposition is achieved; and obtaining a first aperture or openingmeasurement based upon the point of apposition.

In at least one embodiment of a method of the present disclosure, thefirst device is configured as a catheter having a lumen therethrough anddefining a suction/infusion port so that the lumen is in communicationwith the balloon, and wherein the step of inflating is performed byintroducing a fluid through the lumen, through the suction/infusionport, and into the balloon.

In at least one embodiment of a method of the present disclosure, thefirst device further comprises at least one electrode positioned withinthe balloon, and wherein the step of obtaining the first aperture oropening measurement is performed by obtaining a size measurement withinthe balloon using the electrode.

In at least one embodiment of a method of the present disclosure,conductance data is obtained at various stages of balloon inflationduring the inflating step.

In at least one embodiment of a method of the present disclosure, themethod further comprises the step of operating an ablation contactpositioned upon or within a surface of the balloon while the balloon isin contact with the luminal organ to ablate the luminal organ.

In at least one embodiment of a method of the present disclosure, themethod further comprises the step of determining various sizemeasurements of the balloon corresponding to the conductance dataobtained at the various stages of balloon inflation.

In at least one embodiment of a method of the present disclosure, themethod further comprises the step of determining compliance of theluminal organ at the opening or aperture based upon the various sizemeasurements.

In at least one embodiment of a method of the present disclosure, themethod further comprises the step of treating a defect based upon thedetermined compliance of the luminal organ.

In at least one embodiment of a method of the present disclosure, theatrial appendage comprises a left atrial appendage or a right atrialappendage.

In at least one embodiment of a method of the present disclosure, themethod further comprises the step of selecting an appropriately sizedoccluder to occlude the opening of the atrial appendage or the atrialappendage itself based upon the first aperture or opening measurementobtained using the first device or based upon the various sizemeasurements, as applicable.

In at least one embodiment of a method of the present disclosure, themethod comprises the steps of introducing at least part of a firstdevice into a luminal organ so that a balloon of the first device ispositioned at an aperture or opening of the luminal organ at an atrialappendage (referring to the opening of the atrial appendage itself);inflating the balloon at the aperture or opening and obtainingconductance data within the balloon at various stages of ballooninflation using a detector positioned within the balloon; anddetermining various size measurements of the balloon corresponding tothe conductance data obtained at the various stages of ballooninflation.

In at least one embodiment of a method of the present disclosure, themethod further comprises the step of determining compliance of theluminal organ at the aperture or opening based upon the various sizemeasurements.

In at least one embodiment of a method of the present disclosure, thestep of inflating is performed to inflate the balloon so that theballoon contacts the luminal organ at the aperture or opening and toobtain conductance data at various stages of balloon prior to theballoon contacting the luminal organ at the aperture or opening andafter the balloon contacts the luminal organ at the aperture or opening.

In at least one embodiment of a method of the present disclosure,compliance of the luminal organ is determined as being rigid orrelatively rigid based upon at least some of the various sizemeasurements corresponding to conductance data obtained after theballoon contacts the luminal organ at the aperture or opening beingconsistent with one another.

In at least one embodiment of a method of the present disclosure,compliance of the luminal organ is determined as being compliant orrelatively compliant based upon an increase in the various sizemeasurements corresponding to conductance data obtained after theballoon contacts the luminal organ at the aperture or opening beingconsistent with one another.

In at least one embodiment of a method of the present disclosure,compliance of the luminal organ is determined as being rigid orrelatively right based upon a lack of change in the various sizemeasurements corresponding to conductance data obtained after theballoon contacts the luminal organ at the aperture or opening.

In at least one embodiment of a method of the present disclosure, themethod further comprises the step of operating an ablation contactpositioned upon or within a surface of the balloon while the balloon isin contact with the luminal organ to ablate the luminal organ.

In at least one embodiment of a method of the present disclosure, theluminal organ comprises a renal artery, and wherein the method isperformed to treat hypertension.

In at least one embodiment of a method of the present disclosure, themethod comprises the steps of introducing at least part of a firstdevice into a luminal organ so that a balloon of the first device ispositioned at an aperture or opening of the luminal organ at an atrialappendage (referring to the opening of the atrial appendage itself);first inflating the balloon at the aperture or opening and obtainingfirst conductance data within the balloon at various stages of ballooninflation until the balloon contacts the luminal organ at the apertureor opening; second inflating the balloon at the aperture or opening andobtaining second conductance data within the balloon at various stagesof balloon inflation after the balloon contacts the luminal organ at theaperture or opening; and determining various size measurements of theballoon corresponding to the second conductance data.

In at least one embodiment of a method of the present disclosure, themethod further comprises the step of determining compliance of theluminal organ at the aperture or opening based upon the various sizemeasurements.

In at least one embodiment of a method of the present disclosure,compliance of the luminal organ is determined as being compliant orrelatively compliant based upon an increase in the various sizemeasurements corresponding to the second conductance data.

In at least one embodiment of a method of the present disclosure,compliance of the luminal organ is determined as being rigid orrelatively right based upon a lack of change in the various sizemeasurements corresponding to the second conductance data.

In at least one embodiment of a method of the present disclosure, themethod further comprises the step of selecting an appropriately sizedoccluder to occlude the opening of the atrial appendage or the atrialappendage itself based upon the various size measurements.

In at least one embodiment of a method of the present disclosure, themethod comprises the steps of introducing at least part of a firstdevice into an atrial appendage so that a balloon of the first device ispositioned within the atrial appendage; inflating the balloon within theatrial appendage and obtaining conductance data within the balloon atvarious stages of balloon inflation using a detector positioned withinthe balloon; determining various size measurements of the ballooncorresponding to the conductance data obtained at the various stages ofballoon inflation.

In at least one embodiment of a method of the present disclosure, themethod further comprises the step of determining compliance of theatrial appendage based upon the various size measurements.

In at least one embodiment of a method of the present disclosure, themethod further comprises the step of selecting an appropriately sizedoccluder to occlude the atrial appendage based upon the various sizemeasurements.

In at least one embodiment of a method of the present disclosure, themethod comprises introducing at least part of a system comprising aballoon configured for inflation into a luminal organ so that theballoon is adjacent to a valve annulus or opening; introducing a valvedevice within the valve annulus or opening, adjacent the balloon; movingthe valve device within the valve annulus or opening; operating thesystem to obtain measurements of the balloon over time during the stepof moving the valve device within the valve annulus or opening; andgenerating a real-time measurement profile of the measurements overtime.

In at least one embodiment of a method of the present disclosure, themethod is performed to assess left ventricular outflow tract (LVOT)reduction during a valve replacement procedure.

In at least one embodiment of a method of the present disclosure, themeasurements are size measurements, and wherein the method is performedto produce accurate mitral annular sizing measurements.

In at least one embodiment of a method of the present disclosure, themethod further comprises the step of obtaining at least one initialmeasurement of the balloon when adjacent to the valve annulus or openingprior to the step of introducing the valve device within the valveannulus or opening, the at least one initial measurement selected fromthe group consisting of an initial sizing measurement and an initialpressure measurement.

In at least one embodiment of a method of the present disclosure, thereal-time measurement profile can indicate external pinching of theballoon from the valve device when the real-time measurement profileindicates a decrease in size of the balloon.

In at least one embodiment of a method of the present disclosure, anaxis of fluid flow through the valve annulus or opening is defined as anoptimal axis of flow, and wherein the step of moving the valve device isperformed to align the device along and consistent with a perpendicularaxis that is perpendicular to the axis of fluid flow, wherein theperpendicular axis corresponds to an axis of the valve annulus oropening.

In at least one embodiment of a method of the present disclosure, whenthe step of moving the valve device causes an increase in pressurewithin the balloon, which is indicative of improper alignment of thevalve device within the valve annulus or opening.

In at least one embodiment of a method of the present disclosure, themeasurements are pressure measurements, wherein when the step of movingthe valve devices causes a change in pressure within the balloon, andwherein a relative lowest pressure within the balloon is indicative ofproper alignment of the valve device within the valve annulus oropening.

In at least one embodiment of a method of the present disclosure, thereal-time sizing profile corresponds to a degree of left ventricularoutflow tract (LVOT) obstruction over time.

In at least one embodiment of a method of the present disclosure, themeasurements comprise size measurements, the system further comprises atleast two detection electrodes positioned in between two excitationelectrodes, excitation of the two excitation electrodes permitsimpedance measurements to be obtained within the balloon, and theimpedance measurements correspond to the size measurements.

In at least one embodiment of a method of the present disclosure, theincrease in pressure is determined using a pressure sensor or pressuretransducer positioned within the balloon.

In at least one embodiment of a method of the present disclosure, themeasurements comprise pressure measurements, the real-time measurementprofile comprises a real-time pressure measurement profile, the systemfurther comprises a pressure sensor or pressure transducer positionedwithin the balloon, and the step of generating the real-time measurementprofile is performed to generate the real-time pressure measurementprofile.

In at least one embodiment of a method of the present disclosure, thesystem further comprises at least two detection electrodes positioned inbetween two excitation electrodes, the system does not comprise apressure sensor or pressure transducer, and the step of operating thesystem is performed to obtain the measurements corresponding to sizemeasurements of the balloon over time.

In at least one embodiment of a method of the present disclosure, thesystem further comprises a pressure sensor or pressure transducerpositioned within the balloon, the system does not comprise anyexcitation electrodes or any detection electrodes, and the step ofoperating the system is performed to obtain the measurementscorresponding to pressure measurements within the balloon over time.

In at least one embodiment of a method of the present disclosure, thesystem further comprises at least two detection electrodes positioned inbetween two excitation electrodes, the system further comprises apressure sensor or pressure transducer positioned within the balloon,and the step of operating the system is performed to obtain themeasurements corresponding to size measurements of the balloon over timeand pressure measurements within the balloon over time.

In at least one embodiment of a method of the present disclosure, themethod comprises performing a valve replacement procedure using a valvedevice positioned within a valve annulus or opening of a luminal organwhile a system comprising a balloon configured for inflation is at leastpartially introduced into a luminal organ so that the balloon isadjacent to a valve annulus or opening.

In at least one embodiment of a method of the present disclosure, themethod further comprises operating the system to obtain measurements ofthe balloon over time during the valve replacement procedure; andgenerating a real-time measurement profile of the measurements overtime.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows a balloon catheter having impedance measuring electrodessupported in front of the stenting balloon, according to an embodimentof the present disclosure;

FIG. 1B shows a balloon catheter having impedance measuring electrodeswithin and in front of the balloon, according to an embodiment of thepresent disclosure;

FIG. 1C shows a catheter having an ultrasound transducer within and infront of balloon, according to an embodiment of the present disclosure;

FIG. 1D shows a catheter without a stenting balloon, according to anembodiment of the present disclosure;

FIG. 1E shows a guide catheter with wire and impedance electrodes,according to an embodiment of the present disclosure;

FIG. 1F shows a catheter with multiple detection electrodes, accordingto an embodiment of the present disclosure;

FIG. 2A shows a catheter in cross-section proximal to the location ofthe sensors showing the leads embedded in the material of the probe,according to an embodiment of the present disclosure;

FIG. 2B shows a catheter in cross-section proximal to the location ofthe sensors showing the leads run in separate lumens, according to anembodiment of the present disclosure;

FIG. 3 is a schematic of one embodiment of the system showing a cathetercarrying impedance measuring electrodes connected to the dataacquisition equipment and excitation unit for the cross-sectional areameasurement, according to an embodiment of the present disclosure;

FIG. 4A shows the detected filtered voltage drop as measured in theblood stream before and after injection of 1.5% NaCl solution, accordingto an embodiment of the present disclosure;

FIG. 4B shows the peak-to-peak envelope of the detected voltage shown inFIG. 4A, according to an embodiment of the present disclosure;

FIG. 5A shows the detected filtered voltage drop as measured in theblood stream before and after injection of 0.5% NaCl solution, accordingto an embodiment of the present disclosure;

FIG. 5B shows the peak-to-peak envelope of the detected voltage shown inFIG. 5A, according to an embodiment of the present disclosure;

FIG. 6 shows balloon distension of the lumen of the coronary artery,according to an embodiment of the present disclosure;

FIG. 7A shows balloon distension of a stent into the lumen of thecoronary artery, according to an embodiment of the present disclosure;

FIG. 7B shows the voltage recorded by a conductance catheter with aradius of 0.55 mm for various size vessels (vessel radii of 3.1, 2.7,2.3, 1.9, 1.5 and 0.55 mm for the six curves, respectively) when a 0.5%NaCl bolus is injected into the treatment site, according to anembodiment of the present disclosure;

FIG. 7C shows the voltage recorded by a conductance catheter with aradius of 0.55 mm for various size vessels (vessel radii of 3.1, 2.7,2.3, 1.9, 1.5 and 0.55 mm for the six curves, respectively) when a 1.5%NaCl bolus is injected into the treatment site, according to anembodiment of the present disclosure;

FIGS. 8A, 8B, and 8C show various embodiments of devices for sizing apercutaneous valve and/or a valve annulus, according to embodiments ofthe present disclosure;

FIG. 8D shows steps of an exemplary method to size a percutaneous valveand/or a valve annulus, according to the present disclosure;

FIGS. 9A, 9B, and 9C show an exemplary embodiment of a sizing device ofthe present disclosure obtaining sizing data within a luminal organ(FIG. 9A), deflated but having a stent valve positioned around thedevice (FIG. 9B), and inflated to place the stent valve (FIG. 9C),according to embodiments of the present disclosure;

FIG. 9D shows a stent valve positioned within a luminal organ, accordingto an embodiment of the present disclosure;

FIG. 10 shows a block diagram of an exemplary system for sizing apercutaneous valve and/or a valve annulus, according to an embodiment ofthe present disclosure;

FIG. 11 shows calibration data of an exemplary sizing device usingphantoms having known cross-sectional areas, according to an embodimentof the present disclosure;

FIG. 12 shows a side view of a device for sizing a luminal organ orsizing an opening or aperture of a luminal organ, according to thepresent disclosure;

FIG. 13 shows a device for sizing a luminal organ or sizing an openingor aperture of a luminal organ whereby the balloon is positioned withinthe opening or aperture, according to the present disclosure;

FIG. 14 shows a graph of pressure versus balloon cross-sectional areaindicative of sizing of a rigid or relatively rigid luminal organaperture or opening, according to the present disclosure;

FIG. 15 shows a graph of pressure versus balloon cross-sectional areaindicative of sizing of a compliant or relatively compliant luminalorgan aperture or opening, according to the present disclosure;

FIG. 16 shows a side view of a device for sizing a luminal organ orsizing an opening or aperture of a luminal organ at an atrial appendage(namely the opening of the atrial appendage), according to the presentdisclosure;

FIG. 17 shows a device for sizing an atrial appendage whereby theballoon is positioned within the atrial appendage, according to thepresent disclosure;

FIG. 18 shows an occluder positioned within an opening or aperture of aluminal organ at an atrial appendage (namely the opening of the atrialappendage) so to occlude the same, according to the present disclosure;

FIG. 19 shows an occluder positioned within an atrial appendage so toocclude the same, according to the present disclosure;

FIG. 20A shows a sizing device positioned adjacent to a valve annulus oropening, according to the present disclosure;

FIGS. 20B and 20C shows a sizing device positioned adjacent to a valveannulus or opening and a valve device positioned at the valve annulus oropening, according to the present disclosure; and

FIG. 20D shows a distal portion of a sizing device, according to thepresent disclosure.

DETAILED DESCRIPTION

For the purposes of promoting an understanding of the principles of thepresent disclosure, reference will now be made to the embodimentsillustrated in the drawings, and specific language will be used todescribe the same. It will nevertheless be understood that no limitationof the scope of this disclosure is thereby intended.

This present disclosure makes accurate measures of the luminalcross-sectional area of organ stenosis within acceptable limits toenable accurate and scientific stent sizing and placement in order toimprove clinical outcomes by avoiding under or over deployment and underor over sizing of a stent which can cause acute closure or in-stentre-stenosis. In one embodiment, an angioplasty or stent balloon includesimpedance electrodes supported by the catheter in front of the balloon.These electrodes enable the immediate measurement of the cross-sectionalarea of the vessel during the balloon advancement. This provides adirect measurement of non-stenosed area and allows the selection of theappropriate stent size. In one approach, error due to the loss ofcurrent in the wall of the organ and surrounding tissue is corrected byinjection of two solutions of NaCl or other solutions with knownconductivities. In another embodiment impedance electrodes are locatedin the center of the balloon in order to deploy the stent to the desiredcross-sectional area. These embodiments and procedures substantiallyimprove the accuracy of stenting and the outcome and reduce the cost.

Other embodiments make diagnosis of valve stenosis more accurate andmore scientific by providing a direct accurate measurement ofcross-sectional area of the valve annulus, independent of the flowconditions through the valve. Other embodiments improve evaluation ofcross-sectional area and flow in organs like the gastrointestinal tractand the urinary tract.

Embodiments of the present disclosure overcome the problems associatedwith determination of the size (cross-sectional area) of luminal organs,such as, for example, in the coronary arteries, carotid, femoral, renaland iliac arteries, aorta, gastrointestinal tract, urethra and ureter,Embodiments also provide methods for registration of acute changes inwall conductance, such as, for example, due to edema or acute damage tothe tissue, and for detection of muscle spasms/contractions.

As described below, in one preferred embodiment, there is provided anangioplasty catheter with impedance electrodes near the distal end 19 ofthe catheter (i.e., in front of the balloon) for immediate measurementof the cross-sectional area of a vessel lumen during balloonadvancement. This catheter includes electrodes for accurate detection oforgan luminal cross-sectional area and ports for pressure gradientmeasurements. Hence, it is not necessary to change catheters such aswith the current use of intravascular ultrasound. In one preferredembodiment, the catheter provides direct measurement of the non-stenosedarea, thereby allowing the selection of an appropriately sized stent. Inanother embodiment, additional impedance electrodes may be incorporatedin the center of the balloon on the catheter in order to deploy thestent to the desired cross-sectional area. The procedures describedherein substantially improve the accuracy of stenting and improve thecost and outcome as well.

In another embodiment, the impedance electrodes are embedded within acatheter to measure the valve area directly and independent of cardiacoutput or pressure drop and therefore minimize errors in the measurementof valve area. Hence, measurements of area are direct and not based oncalculations with underlying assumptions. In another embodiment,pressure sensors can be mounted proximal and distal to the impedanceelectrodes to provide simultaneous pressure gradient recording.

Catheter

We designed and build the impedance or conductance catheters illustratedin FIGS. 1A-1F. With reference to the exemplary embodiment shown in FIG.1A, four wires were threaded through one of the 2 lumens of a 4 Frcatheter. Here, electrodes 26 and 28, are spaced 1 mm apart and form theinner (detection) electrodes. Electrodes 25 and 27 are spaced 4-5 mmfrom either side of the inner electrodes and form the outer (excitation)electrodes.

In one approach, dimensions of a catheter to be used for any givenapplication depend on the optimization of the potential field usingfinite element analysis described below. For small organs or inpediatric patients the diameter of the catheter may be as small as 0.3mm. In large organs the diameter may be significantly larger dependingon the results of the optimization based on finite element analysis. Theballoon size will typically be sized according to the preferreddimension of the organ after the distension. The balloon may be made ofmaterials, such as, for example, polyethylene, latex,polyestherurethane, or combinations thereof. The thickness of theballoon will typically be on the order of a few microns. The catheterwill typically be made of PVC or polyethylene, though other materialsmay equally well be used. The excitation and detection electrodestypically surround the catheter as ring electrodes but they may also bepoint electrodes or have other suitable configurations. These electrodesmay be made of any conductive material, preferably of platinum iridiumor a carbon-coasted surface to avoid fibrin deposits. In the preferredembodiment, the detection electrodes are spaced with 0.5-1 mm betweenthem and with a distance between 4-7 mm to the excitation electrodes onsmall catheters. The dimensions of the catheter selected for a treatmentdepend on the size of the vessel and are preferably determined in parton the results of finite element analysis, described below. On largecatheters, for use in larger vessels and other visceral hollow organs,the electrode distances may be larger.

Referring to FIGS. 1A, 1B, 1C and 1D, several embodiments of thecatheters are illustrated. The catheters shown contain to a varyingdegree different electrodes, number and optional balloon(s). Withreference to the embodiment shown in FIG. 1A, there is shown animpedance catheter 20 with 4 electrodes 25, 26, 27 and 28 placed closeto the tip 19 of the catheter. Proximal to these electrodes is anangiography or stenting balloon 30 capable of being used for treatingstenosis. Electrodes 25 and 27 are excitation electrodes, whileelectrodes 26 and 28 are detection electrodes, which allow measurementof cross-sectional area during advancement of the catheter, as describedin further detail below. The portion of the catheter 20 within balloon30 includes an infusion port 35 and a pressure port 36.

The catheter 20 may also advantageously include several miniaturepressure transducers (not shown) carried by the catheter or pressureports for determining the pressure gradient proximal at the site wherethe cross-sectional area is measured. The pressure is preferablymeasured inside the balloon and proximal, distal to and at the locationof the cross-sectional area measurement, and locations proximal anddistal thereto, thereby enabling the measurement of pressure recordingsat the site of stenosis and also the measurement of pressure-differencealong or near the stenosis. In one embodiment, shown in FIG. 1A,Catheter 20 advantageously includes pressure port 90 and pressure port91 proximal to or at the site of the cross-sectional measurement forevaluation of pressure gradients. As described below with reference toFIGS. 2A, 2B and 3, in one embodiment, the pressure ports are connectedby respective conduits in the catheter 20 to pressure sensors in thedata acquisition system 100. Such pressure sensors are well known in theart and include, for example, fiber-optic systems, miniature straingauges, and perfused low-compliance manometry.

In one embodiment, a fluid-filled silastic pressure-monitoring catheteris connected to a pressure transducer. Luminal pressure can be monitoredby a low compliance external pressure transducer coupled to the infusionchannel of the catheter. Pressure transducer calibration was carried outby applying 0 and 100 mmHg of pressure by means of a hydrostatic column.

In one embodiment, shown in FIG. 1B, the catheter 39 includes anotherset of excitation electrodes 40, 41 and detection electrodes 42, 43located inside the angioplastic or stenting balloon 30 for accuratedetermination of the balloon cross-sectional area during angioplasty orstent deployment. These electrodes are in addition to electrodes 25, 26,27 and 28.

In one embodiment, the cross-sectional area may be measured using atwo-electrode system. In another embodiment, illustrated in FIG. 1F,several cross-sectional areas can be measured using an array of 5 ormore electrodes. Here, the excitation electrodes 51, 52, are used togenerate the current while detection electrodes 53, 54, 55, 56 and 57are used to detect the current at their respective sites.

The tip of the catheter can be straight, curved or with an angle tofacilitate insertion into the coronary arteries or other lumens, suchas, for example, the biliary tract. The distance between the balloon andthe electrodes is usually small, in the 0.5-2 cm range but can be closeror further away, depending on the particular application or treatmentinvolved.

In another embodiment, shown in FIG. 1C the catheter 21 has one or moreimaging or recording device, such as, for example, ultrasoundtransducers 50 for cross-sectional area and wall thickness measurements.As shown in this embodiment, the transducers 50 are located near thedistal tip 19 of the catheter 21.

FIG. 1D shows an embodiment of the impedance catheter 22 without anangioplastic or stenting balloon. This catheter also possesses aninfusion or injection port 35 located proximal relative to theexcitation electrode 25 and pressure port 36.

With reference to the embodiment shown in FIG. 1E, the electrodes 25,26, 27, 28 can also be built onto a wire 18, such as, for example, apressure wire, and inserted through a guide catheter 23 where theinfusion of bolus can be made through the lumen of the guide catheter37.

With reference to the embodiments shown in FIGS. 1A, 1B, 1C, 1D, 1E and1F, the impedance catheter advantageously includes optional ports 35,36, 37 for suction of contents of the organ or infusion of fluid. Thesuction/infusion port 35, 36, 37 can be placed as shown with the balloonor elsewhere both proximal or distal to the balloon on the catheter. Thefluid inside the balloon can be any biologically compatible conductingfluid. The fluid to inject through the infusion port or ports can be anybiologically compatible fluid but the conductivity of the fluid isselected to be different from that of blood (e.g., NaCl).

In another embodiment (not illustrated), the catheter contains an extrachannel for insertion of a guide wire to stiffen the flexible catheterduring the insertion or data recording. In yet another embodiment (notillustrated), the catheter includes a sensor for measurement of the flowof fluid in the body organ.

System for Determining Cross-Sectional Area and Pressure Gradient

The operation of the impedance catheter 20 is as follows: With referenceto the embodiment shown in FIG. 1A for electrodes 25, 26, 27, 28,conductance of current flow through the organ lumen and organ wall andsurrounding tissue is parallel; i.e.,

$\begin{matrix}{{G\left( {z,t} \right)} = {\frac{{{CSA}\left( {z,t} \right)} \cdot C_{b}}{L} + {G_{p}\left( {z,t} \right)}}} & \left\lbrack {1a} \right\rbrack\end{matrix}$

where G_(p)(z,t) is the effective conductance of the structure outsidethe bodily fluid (organ wall and surrounding tissue), and C_(b) is thespecific electrical conductivity of the bodily fluid which for bloodgenerally depends on the temperature, hematocrit and orientation anddeformation of blood cells and L is the distance between the detectionelectrodes. Equation [1] can be rearranged to solve for cross sectionalarea CSA(t), with a correction factor, α, if the electric field isnon-homogeneous, as

$\begin{matrix}{{{CSA}\left( {z,t} \right)} = {\frac{L}{{\alpha C}_{b}}\left\lbrack {{G\left( {z,t} \right)} - {G_{p}\left( {z,t} \right)}} \right\rbrack}} & \left\lbrack {1b} \right\rbrack\end{matrix}$

where α would be equal to 1 if the field were completely homogeneous.The parallel conductance, G_(p), is an offset error that results fromcurrent leakage. G_(p) would equal 0 if all of the current were confinedto the blood and hence would correspond to the cylindrical model givenby Equation [10]. In one approach, finite element analysis is used toproperly design the spacing between detection and excitation electrodesrelative to the dimensions of the vessel to provide a nearly homogenousfield such that a can be considered equal to 1. Our simulations showthat a homogenous or substantially homogenous field is provided by (1)the placement of detection electrodes substantially equidistant from theexcitation electrodes and (2) maintaining the distance between thedetection and excitation electrodes substantially comparable to thevessel diameter. In one approach, a homogeneous field is achieved bytaking steps (1) and/or (2) described above so that α is equals 1 in theforegoing analysis.

At any given position, z, along the long axis of organ and at any giventime, t, in the cardiac cycle, G_(p) is a constant. Hence, twoinjections of different concentrations and/or conductivities of NaClsolution give rise to two Equations:

C ₁ ⋅CSA(z,t)+L⋅G _(p)(z,t)=L⋅G ₁(z,t)  [2]

and

C ₂ ⋅CSA(z,t)+L⋅G _(p)(z,t)=L⋅G ₂(z,t)  [3]

which can be solved simultaneously for CSA and G_(p) as

$\begin{matrix}{{{CSA}\left( {z,t} \right)} = {L\frac{\left\lbrack {{G_{2}\left( {z,t} \right)} - {G_{1}\left( {z,t} \right)}} \right\rbrack}{\left\lbrack {C_{2} - C_{1}} \right\rbrack}}} & \lbrack 4\rbrack \\{and} & \; \\{{G_{p}\left( {z,t} \right)} = \frac{\left\lbrack {{C_{2} \cdot {G_{1}\left( {z,t} \right)}} - {C_{1} \cdot {G_{2}\left( {z,t} \right)}}} \right\rbrack}{\left\lbrack {C_{2} - C_{1}} \right\rbrack}} & \lbrack 5\rbrack\end{matrix}$

where subscript “1” and subscript “2” designate any two injections ofdifferent NaCl concentrations and/or conductivities. For each injectionk, C_(k) gives rise to G_(k) which is measured as the ratio of the rootmean square of the current divided by the root mean square of thevoltage. The C_(k) is typically determined through in vitro calibrationfor the various NaCl concentrations and/or conductivities. Theconcentration of NaCl used is typically on the order of 0.45 to 1.8%.The volume of NaCl solution is typically about 5 ml, but sufficient todisplace the entire local vascular blood volume momentarily. The valuesof CSA(t) and G_(p)(t) can be determined at end-diastole or end-systole(i.e., the minimum and maximum values) or the mean thereof.

Once the CSA and G_(p) of the vessel are determined according to theabove embodiment, rearrangement of Equation [1] allows the calculationof the specific electrical conductivity of blood in the presence ofblood flow as

$\begin{matrix}{C_{b} = {\frac{L}{{CSA}\left( {z,t} \right)}\left\lbrack {{G\left( {z,t} \right)} - {G_{p}\left( {z,t} \right)}} \right\rbrack}} & \lbrack 6\rbrack\end{matrix}$

In this way, Equation [1b] can be used to calculate the CSA continuously(temporal variation as for example through the cardiac cycle) in thepresence of blood.

In one approach, a pull or push through is used to reconstruct thevessel along its length. During a long injection (e.g., 10-15 s), thecatheter can be pulled back or pushed forward at constant velocity U.Equation [1b] can be expressed as

$\begin{matrix}{{{CSA}\left( {{U \cdot t},t} \right)} = {\frac{L}{C_{b}}\left\lbrack {{G\left( {{U \cdot t},t} \right)} - {G_{p}\left( {U \cdot \left( {t,t} \right)} \right\rbrack}} \right.}} & \lbrack 7\rbrack\end{matrix}$

where the axial position, z, is the product of catheter velocity, U, andtime, t; i.e., z=U⋅t.

For the two injections, denoted by subscript “1” and subscript “2”,respectively, we can consider different time points T1, T2, etc. suchthat Equation [7] can be written as

$\begin{matrix}{{{CSA}_{1}\left( {{U \cdot T_{1}},t} \right)} = {\frac{L}{C_{1}}\left\lbrack {{G_{1}\left( {{U \cdot T_{1}},t} \right)} - {G_{p\; 1}\left( {U \cdot \left( {T_{1},t} \right)} \right\rbrack}} \right.}} & \left\lbrack {8a} \right\rbrack \\{{{CSA}_{1}\left( {{U \cdot T_{1}},t} \right)} = {\frac{L}{C_{2}}\left\lbrack {{G_{2}\left( {{U \cdot T_{1}},t} \right)} - {G_{p\; 1}\left( {U \cdot \left( {T_{1},t} \right)} \right\rbrack}} \right.}} & \left\lbrack {8b} \right\rbrack \\{and} & \; \\{{{CSA}_{2}\left( {{U \cdot T_{2}},t} \right)} = {\frac{L}{C_{1}}\left\lbrack {{G_{1}\left( {{U \cdot T_{2}},t} \right)} - {G_{p\; 2}\left( {U \cdot \left( {T_{2},t} \right)} \right\rbrack}} \right.}} & \left\lbrack {9a} \right\rbrack \\{{{CSA}_{2}\left( {{U \cdot T_{2}},t} \right)} = {\frac{L}{C_{2}}\left\lbrack {{G_{2}\left( {{U \cdot T_{2}},t} \right)} - {G_{p\; 2}\left( {U \cdot \left( {T_{2},t} \right)} \right\rbrack}} \right.}} & \left\lbrack {9b} \right\rbrack\end{matrix}$

and so on. Each set of Equations [8a], [8b] and [9a], [9b], etc. can besolved for GSA₁, G_(p1) and CSA₂, G_(p2), respectively. Hence, we canmeasure the CSA at various time intervals and hence of differentpositions along the vessel to reconstruct the length of the vessel. Inone embodiment, the data on the CSA and parallel conductance as afunction of longitudinal position along the vessel can be exported froman electronic spreadsheet, such as, for example, an Excel file, toAutoCAD where the software uses the coordinates to render a3-Dimensional vessel on the monitor.

For example, in one exemplary approach, the pull back reconstruction wasmade during a long injection where the catheter was pulled back atconstant rate by hand. The catheter was marked along its length suchthat the pull back was made at 2 mm/sec. Hence, during a 10 secondinjection, the catheter was pulled back about 2 cm. The data wascontinuously measured and analyzed at every two second interval; i.e.,at every 4 mm. Hence, six different measurements of CSA and G_(p) weremade which were used to reconstruction the CSA and G_(p) along thelength of the 2 cm segment.

Operation of the impedance catheter 39: With reference to the embodimentshown in FIG. 1B, the voltage difference between the detectionelectrodes 42 and 43 depends on the magnitude of the current (I)multiplied by the distance (D) between the detection electrodes anddivided by the conductivity (C) of the fluid and the cross-sectionalarea (CSA) of the artery or other organs into which the catheter isintroduced. Since the current (I), the distance (L) and the conductivity(C) normally can be regarded as calibration constants, an inverserelationship exists between the voltage difference and the CSA as shownby the following Equations:

$\begin{matrix}{{\Delta \; V} = \frac{I \cdot L}{C \cdot {CSA}}} & \left\lbrack {10a} \right\rbrack \\{or} & \; \\{{CSA} = \frac{G \cdot L}{C}} & \left\lbrack {10b} \right\rbrack\end{matrix}$

where G is conductance expressed as the ratio of current to voltage(I/ΔV). Equation [10] is identical to Equation [1b] if we neglect theparallel conductance through the vessel wall and surrounding tissuebecause the balloon material acts as an insulator. This is thecylindrical model on which the conductance method is used.

As described below with reference to FIGS. 2A, 2B, 3, 4 and 5, theexcitation and detection electrodes are electrically connected toelectrically conductive leads in the catheter for connecting theelectrodes to the data acquisition system 100.

FIGS. 2A and 2B illustrate two embodiments 20A and 20B of the catheterin cross-section. Each embodiment has a lumen 60 for inflating anddeflating the balloon and a lumen 61 for suction and infusion. The sizesof these lumens can vary in size. The impedance electrode electricalleads 70A are embedded in the material of the catheter in the embodimentin FIG. 2A, whereas the electrode electrical leads 70B are tunneledthrough a lumen 71 formed within the body of catheter 70B in FIG. 2B.

Pressure conduits for perfusion manometry connect the pressure ports 90,91 to transducers included in the data acquisition system 100. As shownin FIG. 2A pressure conduits 95A may be formed in 20A. In anotherembodiment, shown in FIG. 2B, pressure conduits 95B constituteindividual conduits within a tunnel 96 formed in catheter 20B. In theembodiment described above where miniature pressure transducers arecarried by the catheter, electrical conductors will be substituted forthese pressure conduits.

With reference to FIG. 3, in one embodiment, the catheter 20 connects toa data acquisition system 100, to a manual or automatic system 105 fordistension of the balloon and to a system 106 for infusion of fluid orsuction of blood. The fluid will be heated to 37-39° or equivalent tobody temperature with heating unit 107. The impedance planimetry systemtypically includes a current unit, amplifiers and signal conditioners.The pressure system typically includes amplifiers and signalconditioners. The system can optionally contain signal conditioningequipment for recording of fluid flow in the organ.

In one preferred embodiment, the system is pre-calibrated and the probeis available in a package. Here, the package also preferably containssterile syringes with the fluids to be injected. The syringes areattached to the machine and after heating of the fluid by the machineand placement of the probe in the organ of interest, the user presses abutton that initiates the injection with subsequent computation of thedesired parameters. The CSA and parallel conductance and other relevantmeasures such as distensibility, tension, etc. will typically appear onthe display panel in the PC module 160. Here, the user can then removethe stenosis by distension or by placement of a stent.

If more than one CSA is measured, the system can contain a multiplexerunit or a switch between CSA channels. In one embodiment, each CSAmeasurement will be through separate amplifier units. The same mayaccount for the pressure channels.

In one embodiment, the impedance and pressure data are analog signalswhich are converted by analog-to-digital converters 153 and transmittedto a computer 157 for on-line display, on-line analysis and storage. Inanother embodiment, all data handling is done on an entirely analogbasis. The analysis advantageously includes software programs forreducing the error due to conductance of current in the organ wall andsurrounding tissue and for displaying the 2D or 3D-geometry of the CSAdistribution along the length of the vessel along with the pressuregradient. In one embodiment of the software, a finite element approachor a finite difference approach is used to derive the CSA of the organstenosis taking parameters such as conductivities of the fluid in theorgan and of the organ wall and surrounding tissue into consideration.In another embodiment, simpler circuits are used; e.g., based on makingtwo or more injections of different NaCl solutions to vary theresistivity of fluid in the vessel and solving the two simultaneousEquations [2] and [3] for the CSA and parallel conductance (Equations[4] and [5], respectively). In another embodiment, the software containsthe code for reducing the error in luminal CSA measurement by analyzingsignals during interventions such as infusion of a fluid into the organor by changing the amplitude or frequency of the current from thecurrent amplifier, which may be a constant current amplifier. Thesoftware chosen for a particular application, preferably allowscomputation of the CSA with only a small error instantly or withinacceptable time during the medical procedure.

In one approach, the wall thickness is determined from the parallelconductance for those organs that are surrounded by air ornon-conducting tissue. In such cases, the parallel conductance is equalto

$\begin{matrix}{G_{p} = \frac{{CSA}_{w} \cdot C_{w}}{L}} & \left\lbrack {11a} \right\rbrack\end{matrix}$

where CSA_(W) is the wall area of the organ and C_(w) is the electricalconductivity through the wall.

This Equation can be solved for the wall CSA_(W) as

$\begin{matrix}{{CSA}_{w} = \frac{G_{p} \cdot L}{C_{w}}} & \left\lbrack {11b} \right\rbrack\end{matrix}$

For a cylindrical organ, the wall thickness, h, can be expressed as

$\begin{matrix}{h = \frac{{CSA}_{w}}{\pi \; D}} & \lbrack 12\rbrack\end{matrix}$

where D is the diameter of the vessel which can be determined from thecircular CSA (D=[4CSA/π]^(1/2)).

When the CSA, pressure, wall thickness, and flow data are determinedaccording to the embodiments outlined above, it is possible to computethe compliance (e.g., ΔCSA/ΔP), tension (e.g., P.r, where P and r arethe intraluminal pressure and radius of a cylindrical organ), stress(e.g., P.r/h where h is the wall thickness of the cylindrical organ),strain (e.g., (C-C_(d))/C_(d) where C is the inner circumference andC_(d) is the circumference in diastole) and wall shear stress (e.g., 4μQ/r³ where μ, Q and r are the fluid viscosity, flow rate and radius ofthe cylindrical organ for a fully developed flow). These quantities canbe used in assessing the mechanical characteristics of the system inhealth and disease.

Method

In one approach, luminal cross-sectional area is measured by introducinga catheter from an exteriorly accessible opening (e.g., mouth, nose oranus for GI applications; or e.g., mouth or nose for airwayapplications) into the hollow system or targeted luminal organ. Forcardiovascular applications, the catheter can be inserted into theorgans in various ways; e.g., similar to conventional angioplasty. Inone embodiment, an 18 gauge needle is inserted into the femoral arteryfollowed by an introducer. A guide wire is then inserted into theintroducer and advanced into the lumen of the femoral artery. A 4 or 5Fr conductance catheter is then inserted into the femoral artery viawire and the wire is subsequently retracted. The catheter tip containingthe conductance electrodes can then be advanced to the region ofinterest by use of x-ray (i.e., fluoroscopy). In another approach, thismethodology is used on small to medium size vessels (e.g., femoral,coronary, carotid, iliac arteries, etc.).

In one approach, a minimum of two injections (with differentconcentrations and/or conductivities of NaCl) are required to solve forthe two unknowns, CSA and G_(p). In another approach, three injectionswill yield three set of values for CSA and G_(p) (although notnecessarily linearly independent), while four injections would yield sixset of values. In one approach, at least two solutions (e.g., 0.5% and1.5% NaCl solutions) are injected in the targeted luminal organ orvessel. Our studies indicate that an infusion rate of approximately 1ml/s for a five second interval is sufficient to displace the bloodvolume and results in a local pressure increase of less than 10 mmHg inthe coronary artery. This pressure change depends on the injection ratewhich should be comparable to the organ flow rate.

In one preferred approach, involving the application of Equations [4]and [5], the vessel is under identical or very similar conditions duringthe two injections. Hence, variables, such as, for example, the infusionrate, bolus temperature, etc., are similar for the two injections.Typically, a short time interval is to be allowed (1-2 minute period)between the two injections to permit the vessel to return to homeostaticstate. This can be determined from the baseline conductance as shown inFIG. 4 or 5. The parallel conductance is preferably the same or verysimilar during the two injections. In one approach, dextran, albumin oranother large molecular weight molecule can be added to the NaClsolutions to maintain the colloid osmotic pressure of the solution toreduce or prevent fluid or ion exchange through the vessel wall.

In one approach, the NaCl solution is heated to body temperature priorto injection since the conductivity of current is temperature dependent.In another approach, the injected bolus is at room temperature, but atemperature correction is made since the conductivity is related totemperature in a linear fashion.

In one approach, a sheath is inserted either through the femoral orcarotid artery in the direction of flow. To access the lower anteriordescending (LAD) artery, the sheath is inserted through the ascendingaorta. For the carotid artery, where the diameter is typically on theorder of 5-5.5 mm, a catheter having a diameter of 1.9 mm can be used,as determined from finite element analysis, discussed further below. Forthe femoral and coronary arteries, where the diameter is typically inthe range from 3.5-4 mm, so a catheter of about 0.8 mm diameter would beappropriate. The catheter can be inserted into the femoral, carotid orLAD artery through a sheath appropriate for the particular treatment.Measurements for all three vessels can be made similarly.

Described here are the protocol and results for one exemplary approachthat is generally applicable to most arterial vessels. The conductancecatheter was inserted through the sheath for a particular vessel ofinterest. A baseline reading of voltage was continuously recorded. Twocontainers containing 0.5% and 1.5% NaCl were placed in temperature bathand maintained at 37°. A 5-10 ml injection of 1.5% NaCl was made over a5 second interval. The detection voltage was continuously recorded overa 10 second interval during the 5 second injection. Several minuteslater, a similar volume of 1.5% NaCl solution was injected at a similarrate. The data was again recorded. Matlab was used to analyze the dataincluding filtering with high pass and with low cut off frequency (1200Hz). The data was displayed using Matlab and the mean of the voltagesignal during the passage of each respective solution was recorded. Thecorresponding currents were also measured to yield the conductance(G=I/V). The conductivity of each solution was calibrated with sixdifferent tubes of known CSA at body temperature. A model using Equation[10] was fitted to the data to calculate conductivity C. The analysiswas carried out in SPSS using the non-linear regression fit. Given C andG for each of the two injections, an excel sheet file was formatted tocalculate the CSA and G_(p) as per Equations [4] and [5], respectively.These measurements were repeated several times to determine thereproducibility of the technique. The reproducibility of the data waswithin 5%. Ultrasound (US) was used to measure the diameter of thevessel simultaneous with our conductance measurements. The detectionelectrodes were visualized with US and the diameter measurements wasmade at the center of the detection electrodes. The maximum differencesbetween the conductance and US measurements were within 10%.

FIGS. 4A, 4B, 5A and 5B illustrate voltage measurements in the bloodstream in the left carotid artery. Here, the data acquisition had asampling frequency of 75 KHz, with two channels—the current injected andthe detected voltage, respectively. The current injected has a frequencyof 5 KH, so the voltage detected, modulated in amplitude by theimpedance changing through the bolus injection will have a spectrum inthe vicinity of 5 KHz.

With reference to FIG. 4A there is shown a signal processed with a highpass filter with low cut off frequency (1200 Hz). The top and bottomportions 200, 202 show the peak-to-peak envelope detected voltage whichis displayed in FIG. 4B (bottom). The initial 7 seconds correspond tothe baseline; i.e., electrodes in the blood stream. The next 7 secondscorrespond to an injection of hyper-osmotic NaCl solution (1.5% NaCl).It can be seen that the voltage is decreased implying increaseconductance (since the injected current is constant). Once the NaClsolution is washed out, the baseline is recovered as can be seen in thelast portion of the FIGS. 4A and 4B. FIGS. 5A and 5B show similar datacorresponding to 0.5% NaCl solutions.

The voltage signals are ideal since the difference between the baselineand the injected solution is apparent and systematic. Furthermore, thepulsation of vessel diameter can be seen in the 0.5% and 1.5% NaClinjections (FIGS. 4 and 5, respectively). This allows determination ofthe variation of CSA throughout the cardiac cycle as outline above.

The NaCl solution can be injected by hand or by using a mechanicalinjector to momentarily displace the entire volume of blood or bodilyfluid in the vessel segment of interest. The pressure generated by theinjection will not only displace the blood in the antegrade direction(in the direction of blood flow) but also in the retrograde direction(momentarily push the blood backwards). In other visceral organs whichmay be normally collapsed, the NaCl solution will not displace blood asin the vessels but will merely open the organs and create a flow of thefluid. In one approach, after injection of a first solution into thetreatment or measurement site, sensors monitor and confirm baseline ofconductance prior to injection of a second solution into the treatmentsite.

The injections described above are preferably repeated at least once toreduce errors associated with the administration of the injections, suchas, for example, where the injection does not completely displace theblood or where there is significant mixing with blood. It will beunderstood that any bifurcation(s) (with branching angle near 90degrees) near the targeted luminal organ can cause an overestimation ofthe calculated CSA. Hence, generally the catheter should be slightlyretracted or advanced and the measurement repeated. An additionalapplication with multiple detection electrodes or a pull back or pushforward during injection will accomplish the same goal. Here, an arrayof detection electrodes can be used to minimize or eliminate errors thatwould result from bifurcations or branching in the measurement ortreatment site.

In one approach, error due to the eccentric position of the electrode orother imaging device can be reduced by inflation of a balloon on thecatheter. The inflation of balloon during measurement will place theelectrodes or other imaging device in the center of the vessel away fromthe wall. In the case of impedance electrodes, the inflation of ballooncan be synchronized with the injection of bolus where the ballooninflation would immediately precede the bolus injection. Our results,however, show that the error due to catheter eccentricity is small.

The CSA predicted by Equation [4] corresponds to the area of the vesselor organ external to the catheter (i.e., CSA of vessel minus CSA ofcatheter). If the conductivity of the NaCl solutions is determined bycalibration from Equation [10] with various tubes of known CSA, then thecalibration accounts for the dimension of the catheter and thecalculated CSA corresponds to that of the total vessel lumen as desired.In one embodiment, the calibration of the CSA measurement system will beperformed at 37° C. by applying 100 mmHg in a solid polyphenolenoxideblock with holes of known CSA ranging from 7.065 mm² (3 mm in diameter)to 1017 mm² (36 in mm). If the conductivity of the solutions is obtainedfrom a conductivity meter independent of the catheter, however, then theCSA of the catheter is generally added to the CSA computed from Equation[4] to give the desired total CSA of the vessel.

The signals are generally non-stationary, nonlinear and stochastic. Todeal with non-stationary stochastic functions, one can use a number ofmethods, such as the Spectrogram, the Wavelet's analysis, theWigner-Ville distribution, the Evolutionary Spectrum, Modal analysis, orpreferably the intrinsic model function (IMF) method. The mean orpeak-to-peak values can be systematically determined by theaforementioned signal analysis and used in Equation [4] to compute theCSA.

Referring to the embodiment shown in FIG. 6, the angioplasty balloon 30is shown distended within the coronary artery 150 for the treatment ofstenosis. As described above with reference to FIG. 1B, a set ofexcitation electrodes 40, 41 and detection electrodes 42, 43 are locatedwithin the angioplasty balloon 30. In another embodiment, shown in FIG.7A, the angioplasty balloon 30 is used to distend the stent 160 withinblood vessel 150.

For valve area determination, it is not generally feasible to displacethe entire volume of the heart. Hence, the conductivity of blood ischanged by injection of hypertonic NaCl solution into the pulmonaryartery which will transiently change the conductivity of blood. If themeasured total conductance is plotted versus blood conductivity on agraph, the extrapolated conductance at zero conductivity corresponds tothe parallel conductance. In order to ensure that the two innerelectrodes are positioned in the plane of the valve annulus (2-3 mm), inone preferred embodiment, the two pressure sensors 36 are advantageouslyplaced immediately proximal and distal to the detection electrodes (1-2mm above and below, respectively) or several sets of detectionelectrodes (see, e.g., FIGS. 1D and 1F). The pressure readings will thenindicate the position of the detection electrode relative to the desiredsite of measurement (aortic valve: aortic-ventricular pressure; mitralvalve: left ventricular-atrial pressure; tricuspid valve: rightatrial-ventricular pressure; pulmonary valve: rightventricular-pulmonary pressure). The parallel conductance at the site ofannulus is generally expected to be small since the annulus consistsprimarily of collagen which has low electrical conductivity. In anotherapplication, a pull back or push forward through the heart chamber willshow different conductance due to the change in geometry and parallelconductance. This can be established for normal patients which can thenbe used to diagnose valvular stensosis.

In one approach, for the esophagus or the urethra, the procedures canconveniently be done by swallowing fluids of known conductances into theesophagus and infusion of fluids of known conductances into the urinarybladder followed by voiding the volume. In another approach, fluids canbe swallowed or urine voided followed by measurement of the fluidconductances from samples of the fluid. The latter method can be appliedto the ureter where a catheter can be advanced up into the ureter andfluids can either be injected from a proximal port on the probe (willalso be applicable in the intestines) or urine production can beincreased and samples taken distal in the ureter during passage of thebolus or from the urinary bladder.

In one approach, concomitant with measuring the cross-sectional area andor pressure gradient at the treatment or measurement site, a mechanicalstimulus is introduced by way of inflating the balloon or by releasing astent from the catheter, thereby facilitating flow through the stenosedpart of the organ. In another approach, concomitant with measuring thecross-sectional area and or pressure gradient at the treatment site, oneor more pharmaceutical substances for diagnosis or treatment of stenosisis injected into the treatment site. For example, in one approach, theinjected substance can be smooth muscle agonist or antagonist. In yetanother approach, concomitant with measuring the cross-sectional areaand or pressure gradient at the treatment site, an inflating fluid isreleased into the treatment site for release of any stenosis ormaterials causing stenosis in the organ or treatment site.

Again, it will be noted that the methods, systems, and cathetersdescribed herein can be applied to any body lumen or treatment site. Forexample, the methods, systems, and catheters described herein can beapplied to any one of the following exemplary bodily hollow systems: thecardiovascular system including the heart; the digestive system; therespiratory system; the reproductive system; and the urogential tract.

Finite Element Analysis: In one preferred approach, finite elementanalysis (FEA) is used to verify the validity of Equations [4] and [5].There are two major considerations for the model definition: geometryand electrical properties. The general Equation governing the electricscalar potential distribution, V, is given by Poisson's Equation as:

∇⋅(C∇V)=-I  [13]

where C, I and V are the conductivity, the driving current density andthe del operator, respectively. Femlab or any standard finite elementpackages can be used to compute the nodal voltages using Equation [13].Once V has been determined, the electric field can be obtained from asE=-∇V.

The FEA allows the determination of the nature of the field and itsalteration in response to different electrode distances, distancesbetween driving electrodes, wall thicknesses and wall conductivities.The percentage of total current in the lumen of the vessel (%I) can beused as an index of both leakage and field homogeneity. Hence, thevarious geometric and electrical material properties can be varied toobtain the optimum design; i.e., minimize the non-homogeneity of thefield. Furthermore, we simulated the experimental procedure by injectionof the two solutions of NaCl to verify the accuracy of Equation [4].Finally, we assessed the effect of presence of electrodes and catheterin the lumen of vessel. The error terms representing the changes inmeasured conductance due to the attraction of the field to theelectrodes and the repulsion of the field from the resistive catheterbody were quantified.

We solved the Poisson's Equation for the potential field which takesinto account the magnitude of the applied current, the location of thecurrent driving and detection electrodes, and the conductivities andgeometrical shapes in the model including the vessel wall andsurrounding tissue. This analysis suggest that the following conditionsare optimal for the cylindrical model: (1) the placement of detectionelectrodes equidistant from the excitation electrodes; (2) the distancebetween the current driving electrodes should be much greater than thedistance between the voltage sensing electrodes; and (3) the distancebetween the detection and excitation electrodes is comparable to thevessel diameter or the diameter of the vessel is small relative to thedistance between the driving electrodes. If these conditions aresatisfied, the equipotential contours more closely resemble straightlines perpendicular to the axis of the catheter and the voltage dropmeasured at the wall will be nearly identical to that at the center.Since the curvature of the equipotential contours is inversely relatedto the homogeneity of the electric field, it is possible to optimize thedesign to minimize the curvature of the field lines. Consequently, inone preferred approach, one or more of conditions (1)-(3) describedabove are met to increase the accuracy of the cylindrical model.

Theoretically, it is impossible to ensure a completely homogeneous fieldgiven the current leakage through the vessel wall into the surroundingtissue. We found that the iso-potential line is not constant as we moveout radially along the vessel as stipulated by the cylindrical model. Inone embodiment, we consider a catheter with a radius of 0.55 mm whosedetected voltage is shown in FIGS. 7B and 7C for two different NaClsolutions (0.5% and 1.5%, respectively). The origin corresponds to thecenter of the catheter. The first vertical line 220 represents the innerpart of the electrode which is wrapped around the catheter and thesecond vertical line 221 is the outer part of the electrode in contactwith the solution (diameter of electrode is approximately 0.25 mm). Thesix different curves, top to bottom, correspond to six different vesselswith radii of 3.1, 2.7, 2.3, 1.9, 1.5 and 0.55 mm, respectively. It canbe seen that a “hill” occurs at the detection electrode 220, 221followed by a fairly uniform plateau in the vessel lumen followed by anexponential decay into the surrounding tissue. Since the potentialdifference is measured at the detection electrode 220, 221, oursimulation generates the “hill” whose value corresponds to theequivalent potential in the vessel as used in Equation [4]. Hence, foreach catheter size, we varied the dimension of the vessel such thatEquation [4] is exactly satisfied. Consequently, we obtained the optimumcatheter size for a given vessel diameter such that the distributivemodel satisfies the lumped Equations (Equation [4] and [5]). In thisway, we can generate a relationship between vessel diameter and catheterdiameter such that the error in the CSA measurement is less than 5%. Inone embodiment, different diameter catheters are prepackaged and labeledfor optimal use in certain size vessel. For example, for vesseldimension in the range of 4-5 mm, 5-7 mm or 7-10 mm, our analysis showsthat the optimum diameter catheters will be in the range of 0.91.4,1.4-2 or 2-4.6 mm, respectively. The clinician can select theappropriate diameter catheter based on the estimated vessel diameter ofinterest. This decision will be made prior to the procedure and willserve to minimize the error in the determination of lumen CSA.

Percutaneous Valve and Valve Annulus Sizing

In addition to the foregoing, the disclosure of the present applicationdiscloses various devices, systems, and methods for sizing apercutaneous valve and/or a valve annulus and placing replacement valveswithin a luminal organ using a balloon.

An exemplary embodiment of a device for sizing a valve annulus 500 ofthe present disclosure is shown in FIG. 8A. As shown in FIG. 8A, anexemplary device 500 comprises a catheter 39 and a balloon 30 positionedthereon at or near the tip 19 (distal end) of catheter 39 so that anygas and/or fluid injected through catheter 20 into balloon 30 by way ofa suction/infusion port 35 will not leak into a patient's body when sucha device 500 is positioned therein.

As shown in FIGS. 8A and 8B, device 500 comprises a detector 502,wherein detector 502, in at least one embodiment, comprises a tetrapolararrangement of two excitation electrodes 40, 41 and two detectionelectrodes 42, 43 located inside balloon 30 for accurate determinationof the balloon 30 cross-sectional area during sizing of a valve annulus.Such a tetrapolar arrangement (excitation, detection, detection, andexcitation, in that order) as shown in FIG. 8A would allow sizing of thespace within balloon 30, including the determination of balloon 30cross-sectional area. As shown in FIG. 8A, device 500 comprises acatheter 39 (an exemplary elongated body), wherein balloon 30 ispositioned thereon at or near the tip 19 (distal end) of catheter 39. Inaddition, an exemplary embodiment of a device 500, as shown in FIG. 8A,comprises a pressure transducer 48 capable of measuring the pressure ofa gas and/or a liquid present within balloon 30. Device 500 also has asuction/infusion port 35 defined within catheter 39 inside balloon 30,whereby suction/infusion port 35 permits the injection of a gas and/or afluid from a lumen of catheter 39 into balloon 30, and further permitsthe removal of a gas and/or a fluid from balloon 30 back into catheter39.

FIG. 8C, as referenced above, shows another exemplary embodiment of adevice 500 of the present disclosure. FIG. 8C comprises several of thesame components shown in the embodiments of a device 500 of the presentdisclosure shown in FIGS. 8A and 8B, but as shown in FIG. 8C, balloon 30does not connect to catheter 39 at both relative ends of balloon 30.Instead, balloon 30 is coupled to catheter 39 proximal to electrodes 40,41, 42, and 43, and is not coupled to catheter 39 distal to saidelectrodes. In addition, the exemplary embodiment of device 500 shown inFIG. 8C comprises a data acquisition and processing system 220 coupledthereto. The exemplary embodiments of devices 500 shown in FIGS. 8A and8C are not intended to be the sole embodiments of said devices 500, asvarious devices 500 of the present disclosure may comprise additionalcomponents as shown in various other figures and described herein.

Various exemplary embodiments of devices 500 of the present disclosuremay be used to size a valve annulus as follows. In at least oneembodiment of a method to size a valve annulus of the presentdisclosure, method 600, as shown in FIG. 8D, comprises the steps ofintroducing at least part of a sizing device into a luminal organ at avalve annulus (an exemplary introduction step 602), wherein the sizingdevice 500 comprises a detector 502 and a pressure transducer 48 withina balloon 30 at or near a distal end 19 of sizing device 500. Method 600then comprises the steps of inflating balloon 30 until a thresholdpressure is detected by pressure transducer 48 within balloon 30 (anexemplary inflation step 604), and obtaining a first valve annulusmeasurement using detector 504 (an exemplary measurement step 606). Inat least one embodiment, balloon 30 has a larger diameter than the valveannulus to be sized, so that when balloon 30 is initially inflated(inflation step 604), the diameter of balloon 30 will increase but thepressure of the balloon 30 will remain small because of excess balloon30. Once the diameter of balloon 30 reaches the border of the annulus,the measured balloon pressure will begin to rise. In an exemplaryinflation step 604, inflation step 604 comprises the step of introducinga fluid into a lumen of device 500, through a suction/infusion port 35,and into balloon 30. At the point of apposition (significant pressurerise, also referred to herein as a “threshold pressure”), the size ofballoon 30 will correspond to the size of the annulus and hence thedesired measurement. When a threshold pressure is reached within balloon30, measurement step 606 may be performed to obtain an optimal firstvalve annulus measurement.

An exemplary measurement step 606 of method 600, in at least oneembodiment, comprises measuring a balloon 30 cross-sectional area usingdetector 502. In an exemplary embodiment, measurement step 606 isperformed when a threshold pressure is present within balloon 30. In atleast one embodiment, the balloon 30 cross-sectional area is determinedfrom a conductance measurement of a fluid present within balloon 30obtained by detector 502, a known conductivity of the fluid, and a knowndistance between detection electrodes 41, 42.

FIG. 9A shows an exemplary embodiment of a sizing device 500 positionedwithin a luminal organ 550 at a valve annulus 552. Device 500 is shownin FIG. 9A with an inflated balloon 30, with electrodes 40, 41, 42, 43defined within the figure. At the time a threshold pressure withinballoon 30 is identified by pressure transducer 48, electrodes 40, 41,42, 43 (a detector 502 as referenced herein) may operate to obtain afirst valve annulus measurement, such as a valve annulus cross-sectionalarea, corresponding to the cross-sectional area of balloon 30. Such ameasurement (measurement step 606) is a more precise valve annulusmeasurement that can be obtained either visually (under fluoroscopy) orusing pressure alone.

After measurement step 606 is performed, and in at least one embodimentof a method 600 of the present disclosure, method 600 further comprisesthe steps of withdrawing sizing device 500 from luminal organ 550 (anexemplary device withdrawal step 608). In an exemplary device withdrawalstep 608, device withdrawal step 608 comprises the step of removingfluid from balloon 30, through suction/infusion port 35, and into thelumen of device 500, to deflate balloon 30. In at least one embodimentof method 600 comprises the optional steps of positioning a stent valve560 (as shown in FIGS. 9B-9D) upon balloon 30 (an exemplary stent valvepositioning step 610), reintroducing at least part of device 500 backinto luminal organ 550 at valve annulus 552 (an exemplary reintroductionstep 612), and reinflating balloon 30 to a desired inflation to placestent valve 560 within valve annulus 552 (an exemplary stent valveplacement step 614).

At least some of the aforementioned steps of method 600 are also shownin FIGS. 9B-9D. As shown in FIG. 9B, and once the valve annulus has beensized using method 600 of the present disclosure, an appropriate sizestent can then be placed within luminal organ 550. Detector 502, after astent valve 560 has been positioned upon balloon 30, can then sizeballoon 30 carrying stent valve 560. FIG. 9B shows at least part ofdevice 500 having stent valve 560 positioned upon a relatively orcompletely deflated balloon 30, and FIG. 9C shows the same device 500having an inflated balloon 30 to place stent valve 560 within luminalorgan 550. Balloon 30, as shown in FIG. 9C, is inflated until thedesired size of stent valve 560 is reached to ensure the desiredapposition. Since the wall thickness of balloon 30 is known, the size ofballoon 30, when inflated, will reflect the size of stent valve 560.Device 500 can then be removed from luminal organ 550 (an exemplarydevice rewithdrawal step 616), wherein stent valve 560 remainspositioned within luminal organ 550 at valve annulus 552.

FIG. 9B is also indicative of sizing a percutaneous valve 554 itself,whereby the percutaneous valve flaps are visible in FIG. 9B. Such sizingmay be performed using an exemplary method 600 of the presentdisclosure, whereby an exemplary inflation step 604 comprises inflatingballoon 30 at the site of percutaneous valve 554 until a thresholdpressure is met, and whereby an exemplary measurement step 606 comprisesobtaining a percutaneous valve opening measurement using detector 504.

An exemplary system for sizing a percutaneous valve and/or a valveannulus of the present disclosure is shown in the block diagram shown inFIG. 10. As shown in FIG. 10, system 700 comprises a device 500, a dataacquisition and processing system 220 coupled thereto, and a currentsource 218 coupled to a detector 502 and a pressure transducer 48 ofdevice 500. Device 500, as shown in FIG. 10, may comprise a catheter 39(an exemplary elongated body) having a balloon 30 coupled thereto,wherein detector 502 and pressure transducer 48 are positioned alongcatheter 39 within balloon 30. A suction/infusion port 35 may also bedefined within catheter 39, as referenced herein, to facilitate themovement of a fluid in and out of balloon 30 from catheter 39.

As referenced herein, a modified version of Ohm's law may be used,namely:

CSA=(G/L)/α  [14]

wherein CSA is the cross-sectional area of balloon 30, G is theelectrical conductance given by a ratio of current and voltage drop(I/V, wherein I represents injected current and V is the measuredvoltage drop along detection electrodes 41, 42), L is a constant for thelength of spacing between detection electrodes 41, 42 of sizing device500, and α is the electrical conductivity of the fluid within balloon30. Equation [14] can then be used to provide CSA in real time given theconductivity of fluid used to inflate the balloon (such as, for example,half normal saline (0.9% NaCl)) and half contrast (iodine, etc.), themeasure conductance (G) and the known distance L.

A typical calibration curve of an impedance balloon 30 is shown in FIG.11. As shown in FIG. 11, the slope of the line provides the conductivity(α) of fluid within balloon. The solid line shown in FIG. 11 has alinear fit of the form y=1.00664×x-0.4863, wherein R²=0.99. Calibration,in at least this example, was performed using various phantoms havingknown CSAs.

The present disclosure also includes disclosure of devices, systems, andmethods to size various luminal organs and openings or apertures withinluminal organs, including, but not limited to, renal artery sizing.Renal arteries, as well as various other luminal organs, can havedifferent dimensions (diameters, cross-sectional areas, etc.) frompatient to patient, and use of various balloon 30 embodiments may bechosen depending on the sizing procedure and/or treatment procedureperformed. Furthermore, various openings or apertures within luminalorgans can be more or less compliant or rigid that others, and anunderstanding or knowledge of the relative compliance or rigidity mayimpact a potential course of patient treatment or care.

The present disclosure includes significant disclosure regarding sizingof luminal organs using impedance by obtaining conductance data andusing said data to obtain luminal organ parameters such ascross-sectional area and diameter. Additional disclosure is providedabove regarding obtaining similar data within a valve annulus, anexemplary opening or aperture (as described in further detail below)within a luminal organ. As such, the present disclosure includesdisclosure of devices, systems, and methods to obtain conductance datauseful to determine luminal organ opening or aperture 1310 information,such as diameters and/or cross-sectional areas.

Devices 500 and systems 700 of the present disclosure include balloons30 having various impedance sensors (an exemplary detector 502, aspreviously referenced herein, such as devices comprising electrodes 40,41, 42, and 43 (whereby electrodes 40 and 41 are excitation electrodesand electrodes 42 and 43 are detection electrodes), comprisingelectrodes 25, 26, 27, and 28 (whereby electrodes 25 and 28 areexcitation electrodes and electrodes 26 and 27 are detectionelectrodes), and/or comprising electrodes 51, 52, 53, 54, 55, 56, and 57(whereby electrodes 51 and 57 are excitation electrodes and electrodes52, 53, 54, 55, and 56 are detection electrodes), for example,positioned on and/or within a surface 1200 of balloon 30. FIG. 12 showsan exemplary device 500 embodiment, identifying detector 502 ascomprising electrodes 40, 41, 42, 43, by way of example. Balloon 30 canbe coupled to catheter 20, 21, 22, or 39, as referenced herein, withcatheter 20 being the exemplary catheter shown in FIG. 12. Various wires1202, as shown in FIG. 12, can be used to connect the various electrodes40, 41, 42, and 43 (or other electrodes as referenced herein) to, forexample, a data acquisition and processing system 100 or 220 asreferenced herein.

Said electrodes 40, 41, 42, and 43, when operated consistent with thepresent disclosure, can be used to indicate whether or not a balloon 30has inflated to the extent of making physical contact with a wall 1300of a luminal organ 150 (such as a blood vessel, heart, or other luminalorgan of the present disclosure) For example, conductance measurementsobtained using electrodes 40, 41, 42, 43 while balloon 30 is not incontact with wall 1300 of luminal organ will differ from conductancemeasurements obtained using the same electrodes 40, 41, 42, 43 whileballoon 30 is in contact with wall 1300 of luminal organ 150, such aswhen one or more of electrodes 40, 41, 42, 43 contact wall 1300.

Renal artery sizing, for example, can factor into an appropriatetreatment/procedure to treat hypertension using renal ablation. Surgicalapproaches have been shown to be effective, but they are of coursetraumatic, noting that an intravascular approach would be preferred.Various embodiments of devices 500 of the present disclosure can be usedto obtain accurate sizing information (diameter and/or cross-sectionalarea) of renal arteries, and in some embodiments, the same devices 500can be used for ablation. For example, FIG. 12 shows a device 500embodiment having an ablation contact 1250 positioned on and/or within asurface 1200 of balloon 30. Operation of ablation contact 1250 can alsobe controlled using data acquisition and processing system 220, withablation contact 1250 being powered via wire 1202. As referenced above,balloon 30 can be inflated to the point where it is known that balloon30 is contacting a vessel wall 150. Ablation contact 1250 can then beoperated to perform renal ablation, for example, to treat hypertension.Conversely, devices 500 without ablation contacts 1250 can be used toprovide sizing information, while other ablation devices known ordeveloped in the medical arts can perform the ablation. As such, thepresent disclosure includes disclosure of devices, systems, and methodsto perform renal ablation and to treat hypertension.

Intraseptal ventricular defect (ISD) is a congenital heart defect wherethe septum of the heart is not completely formed. Determining whether ornot the septum is rigid or compliant can be an important indicator as tothe potential treatment of said defect, as a more compliant septum canbe treated differently as compared to a more rigid septum.

In at least one method of obtaining a size parameter of a luminal organopening or aperture 1310, such as a septum of the heart, a balloon 30 ofa device 500 of the present disclosure is positioned within said openingor aperture 1310, such as shown in FIG. 13. Balloon 30, in such a device500 embodiment, would comprise a compliant balloon 30. Should saidopening or aperture 1310 (referring to the luminal organ at the openingor aperture and/or adjacent tissue forming the opening or aperture) berigid or relatively rigid, inflation of balloon 30 and obtaining variousconductance measurements (used to determine a luminal organ parameter,such as diameter or cross-sectional area as referenced herein), wouldresult in a series of measurements whereby a) inflation of balloon 30prior to balloon 30 contacting a luminal organ 150 wall 1300 within saidopening or aperture would identify increasingly larger cross-sectionalareas (corresponding to increasing larger cross-sectional areas ofballoon 30), and b) when balloon 30 is inflated to the point ofcontacting said wall 1300, additional conductance measurements (used todetermine a luminal organ parameter, such as diameter or cross-sectionalarea as referenced herein) would generally result in a consistent/steadycross-sectional area measurement, as the rigid or relatively rigidopening or aperture 1310 would prevent further balloon 30 distensionwithin said opening or aperture 1310. This is generally depicted in FIG.14, noting that an absolute size (cross-sectional area) of opening oraperture 1310 can be obtained.

Conversely, and should opening or aperture 1310 be compliant orrelatively compliant, inflation of balloon 30 and obtaining variousconductance measurements (used to determine a luminal organ parameter,such as diameter or cross-sectional area as referenced herein), wouldalso result in a series of measurements whereby inflation of balloon 30prior to balloon 30 contacting a luminal organ 150 wall 1300 within saidopening or aperture 1310 would identify increasingly largercross-sectional areas (corresponding to increasing largercross-sectional areas of balloon 30). However, when balloon 30 isinflated to the point of contacting said wall 1300, additionalconductance measurements (used to determine a luminal organ parameter,such as diameter or cross-sectional area as referenced herein) wouldcontinue to identify larger cross-sectional areas, for example, butwould do so at a lesser rate, and would ultimately taper off, indicatingthat said opening or aperture 1310 has stretched to its general limitbased upon balloon inflation. This is generally depicted in FIG. 15. Assuch, the present disclosure includes disclosure of devices, systems,and methods to obtain sizing and/or compliance data regarding a luminalorgan 150 opening or aperture 1310, useful, for example, to treat aseptal defect, such as an intraseptal ventricular defect.

The present disclosure also includes disclosure of various otheropenings of luminal organs, including, but not limited to, the openingof an atrial appendage (such as a left atrial appendage (LAA) or a rightatrial appendage (RAA)), as well as sizing the LAA or RAA itself.

In at least one method of obtaining a size parameter of a luminal organopening or aperture 1310, such as the opening or aperture 1310 of a anatrial appendage 151 (such as a left atrial appendage or a right atrialappendage), a balloon 30 of a device 500 of the present disclosure ispositioned within said opening or aperture 1310, such as shown in FIG.16, wherein the luminal organ 150 comprises a heart having an atrialappendage 151. Balloon 30, in such a device 500 embodiment, wouldcomprise a compliant balloon 30. Should said opening or aperture 1310(referring to the luminal organ 150 at the opening or aperture 1310 ofthe atrial appendage 151) be rigid or relatively rigid, inflation ofballoon 30 and obtaining various conductance measurements (used todetermine a luminal organ parameter, such as diameter or cross-sectionalarea as referenced herein), would result in a series of measurementswhereby a) inflation of balloon 30 prior to balloon 30 contacting aluminal organ 150 wall 1300 within said opening or aperture 1310 wouldidentify increasingly larger cross-sectional areas (corresponding toincreasing larger cross-sectional areas of balloon 30), and b) whenballoon 30 is inflated to the point of contacting said wall 1300,additional conductance measurements (used to determine a luminal organparameter, such as diameter or cross-sectional area as referencedherein) would generally result in a consistent/steady cross-sectionalarea measurement, as the rigid or relatively rigid opening or aperture1310 would prevent further balloon 30 distension within said opening oraperture 1310. This is generally depicted in FIG. 14, noting that anabsolute size (cross-sectional area) of opening or aperture 1310 can beobtained. In such an embodiment, an absolute size (cross-sectional area)of an opening or aperture 1310 of an atrial appendage 151 can beobtained using an exemplary system 700 or device 500 of the presentdisclosure. Furthermore, the opening or aperture 1310 of the atrialappendage 151 can be sized using any number of devices, systems, and ormethods of the present disclosure as referenced herein.

In at least one method of obtaining a size parameter of a luminal organopening or aperture 1310, such as an atrial appendage 151 itself, aballoon 30 of a device 500 of the present disclosure is positionedwithin the atrial appendage 151 itself, such as shown in FIG. 17.Balloon 30, in such a device 500 embodiment, would comprise a compliantballoon 30. Should the atrial appendage 151 be rigid or relativelyrigid, inflation of balloon 30 and obtaining various conductancemeasurements (used to determine a luminal organ parameter, such asdiameter or cross-sectional area as referenced herein), would result ina series of measurements whereby a) inflation of balloon 30 prior toballoon 30 contacting a luminal organ 150 wall 1300 within the atrialappendage 151 would identify increasingly larger cross-sectional areas(corresponding to increasing larger cross-sectional areas of balloon30), and b) when balloon 30 is inflated to the point of contacting saidwall 1300 of the atrial appendage 151, additional conductancemeasurements (used to determine a luminal organ parameter, such asdiameter or cross-sectional area as referenced herein) would generallyresult in a consistent/steady cross-sectional area measurement, as therigid or relatively rigid atrial appendage 151 would prevent furtherballoon 30 distension within said atrial appendage 151. This isgenerally depicted in FIG. 14, noting that an absolute size(cross-sectional area) of the atrial appendage 151 can be obtained. Insuch an embodiment, an absolute size (cross-sectional area) of an atrialappendage 151 itself can be obtained using an exemplary system 700 ordevice 500 of the present disclosure. Furthermore, and as an atrialappendage 151 is an exemplary luminal organ 150 of the presentdisclosure, the atrial appendage 151 can be sized using any number ofdevices, systems, and or methods of the present disclosure as referencedherein.

Sizing of the atrial appendage 151 or an opening or aperture 1310 of theatrial appendage 151 can be performed so that an occluder 152 of adesired size can be positioned at the opening or aperture 1310 of theatrial appendage 151, such as shown in FIG. 18, or within the atrialappendage 151 itself, such as shown in FIG. 19. By obtaining size dataof the opening or aperture 1310 of the atrial appendage 151 and/or theatrial appendage itself, an occluder 152 of an appropriate and safe sizecan be selected for insertion into the said opening or aperture 1310 orsaid atrial appendage 151. By using an appropriately-sized occluder 152,the opening or aperture 1310 of the atrial appendage 151 or said atrialappendage 151 itself can be effectively occluded without exertingunnecessary force against said opening or aperture 1310 of the atrialappendage 151 or said atrial appendage 151 itself, which couldpotentially cause rupture of the atrial appendage 151.

Such embodiments of devices 500 of the present disclosure have severaladvantages. First, electrodes 40, 41, 42, and 43 are positioned alongcatheter 39 within balloon 30, so minimal risk to damage of saidelectrodes arises. Second, and since balloon 30 insulates the electricfield generated by excitation electrodes 40, 41, there is no parallelconductance and hence no need for two injections to obtain a desiredmeasurement. In addition, said devices 500 incorporate the ability tosize a valve and/or a valve annulus and can also deliver a stent valve560 as referenced herein. Using Equation [14] for example, real-timemeasurements of CSA can be obtained as desired, with no additionalprocedures required by a physician. The sizing results are quiteaccurate (as shown in FIG. 11), providing additional confidence of thesizing measurements without the need for echocardiograms, MRIs, or otherexpensive imaging mechanisms.

The present disclosure includes disclosure of a novel sizingvalvuloplasty conductance balloon catheter system, such as sizingdevices 500 of the present disclosure including those shown in FIGS.9A-9D and otherwise referenced herein, that serve as a universal balloon(balloon 30) for valve sizing prior to implant (TAVR, TMVR, etc.), suchas the implantation of a stent valve 560 as referenced herein. Thepresent disclosure further discloses the use of this technology toaccurately measure and display real-time left ventricular outflow tract(LVOT) obstruction during mitral valve (valve device 560, for example)implant delivery. Such a use would allow LVOT reduction to be assessedduring TMVR since a sizing profile can be obtained in real-time and anyexternal pinching on the LVOT balloon can be detected as a decrease inLVOT annular profile. This would be extremely useful in TMVR todiagnose/prevent LVOT obstruction.

Current TMVR procedures already invoke an arterial access through a 6Fr. sheath which would accommodate our sizing device 500. In oneembodiment, such as shown in FIGS. 20A, 20B, and 20C, a 6Fr compatiblevalvuloplasty sizing device 500 can be used, with multiple detectionelectrodes 42, 43 (whereby electrodes 42 and 43 represent detectionelectrodes that can be used in various multiples of one another), suchas at 0.5 cm intervals or other intervals as may be desired, and usingone set/pair of excitation electrodes 40, 41. The diameter of the sizingballoon 30, in such an embodiment, will accommodate 23-25 mm with lengthof balloon 30 in the range of 4-6 cm. FIG. 20D shows a distal portion ofan exemplary sizing device,

FIG. 20A shows a sizing device 500, such as referenced above andotherwise herein, positioned adjacent to a valve annulus or opening 552of a luminal organ 550. FIGS. 20B and 20C show the sizing device 500,with balloon 30 inflated, positioned at the same location as noted inFIG. 20A, but now with a valve device 560 positioned within the valveannulus or opening 552, with valve device at a relatively largerexpansion configuration in FIG. 20B as compared to FIG. 20C. Sizingdevice 500, when operated to obtain size measurements using impedance,as referenced herein (cross-sectional area, diameter, etc., of balloon30, corresponding to the general boundary of balloon 30 formed by theluminal organ 550 at the location of balloon 30 (such as at the locationof valve annulus or opening 552 or adjacent thereto)), can create areal-time sizing profile (namely sizing data over time), and anyexternal pinching on the LVOT balloon can be detected as a decrease inLVOT annular profile. FIG. 20D shows a distal portion of an exemplarysizing device of the present disclosure, with features/components asreferenced herein.

Desired alignment or general positioning of valve device 560 withinvalve annulus or opening 552 can also be performed/achieved with respectto the foregoing. As shown in FIG. 20B, an axis of fluid flow 2000though valve device 560 corresponding to positioning of valve device 560within the valve annulus or opening 552 is not proper, as compared toFIG. 20C, whereby the axis of fluid flow 2000 though valve device 560corresponding to positioning of valve device 560 within the valveannulus or opening 552 is proper (as indicative of perpendicular axis2002, which is perpendicular to axis of fluid flow 2000), as desiredalignment or positioning of valve device 560 would result in valvedevice 560 being aligned with perpendicular axis 2002, as shown in FIG.20C, as may be desired. It is understood that a valve device 560 may nothave a specific alignment axis, but in certain instances, such as shownin FIGS. 20B and 20C, a valve device 560 may need or require a properalignment or placement, such as shown in FIG. 20C, as compared to thatas shown in FIG. 20B. Perpendicular axis 2002 can generally correspondto a valve annulus or opening 552, whereby axis 2002 aligns with valveannulus or opening 552 as shown in FIG. 20C, but does not so align asshown in FIG. 20B.

Furthermore, and as shown in FIGS. 20B and 20C, a potential or actualcontact location 2004 can or may exist between valve device 560 andsizing device 500. As shown in FIG. 20B, contact location 2004 is anactual contact location (or a relatively higher degree of contact)between valve device 560 and sizing device 500, whereby valve device 560contacts sizing device 500 when balloon 30 of sizing device 500 isinflated, which can be indicative of improper alignment or positioningof valve device 560 within valve annulus or opening 552. Conversely, andas shown in FIG. 20C, contact location 2004 is a potential contactlocation (or a relatively lower degree of contact as compared to thatshown in FIGS. 20B) between valve device 560 and sizing device 500,whereby valve device 560 either does not contact sizing device 500 orcontacts sizing device 500 when balloon 30 of sizing device 500 isinflated, which can be indicative of proper alignment or positioning ofvalve device 560 within valve annulus or opening 552.

In view of the same, the present disclosure includes disclosure ofmethods to assess LVOT reduction during a valve replacement procedure,detected as a decrease in an annular profile, corresponding to size dataobtained using sizing device 500.

In addition to the foregoing, the present disclosure also includesdisclosure relating to sensing the obstruction, such as by sensing theobstruction using a pressure sensor (an exemplary pressure transducer 48of the present disclosure, such as shown in FIG. 20D) internal to theballoon 30 of sizing device 500. For example, a detected pressure wouldincrease if a transcatheter mitral implant would impinge on the balloon,whereby squeezing (or otherwise applying pressure to the outside of theballoon) would compress a fluid within the balloon and increase thepressure. So, as referenced above, impedance can be used to obtainsizing data (such as by using a detector 502 of a sizing device 500having multiple electrodes 40, 41, 42, 43, for example), which can beused to create a sizing profile and indicate whether or not a valvedevice 560 (such as a transcatheter mitral implant or other devicesreferenced herein) is impinging balloon 30 of sizing device 500, andpressure, such as by way of detected changes in pressure within balloon30, can also be an indication of whether or not valve device 560impinges balloon 30. In view of the same, the present disclosureincludes disclosure of a device (such as a sizing device 500), which mayor may not include electrodes 40, 41, 42, 43, but does contain apressure transducer 48 within a balloon 30, so that changes in pressure,such as by way of impingement of balloon 30 by a valve device 560, canbe detected over time (such as by way of generating a profile ofpressures over time and detecting changes in pressure during placementof valve device 560 within the body, so that proper placement and/oralignment of valve device 560 can be achieved, as discussed above.Undesired pressure applied to the outside of balloon 30, detected bypressure transducer 48, can indicate improper placement and/or alignmentof valve device 560 within the body.

Again, it is noted that the various devices, systems, and methodsdescribed herein can be applied to any body lumen or treatment site. Forexample, the devices, systems, and methods described herein can beapplied to any one of the following exemplary bodily hollow organs: thecardiovascular system including the heart, the digestive system, therespiratory system, the reproductive system, and the urogenital tract.

While various embodiments of devices, systems, and methods for measuringa luminal organ opening or aperture using a balloon sizing device havebeen described in considerable detail herein, the embodiments are merelyoffered by way of non-limiting examples of the disclosure describedherein. It will therefore be understood that various changes andmodifications may be made, and equivalents may be substituted forelements thereof, without departing from the scope of the disclosure.Indeed, this disclosure is not intended to be exhaustive or to limit thescope of the disclosure.

Further, in describing representative embodiments, the disclosure mayhave presented a method and/or process as a particular sequence ofsteps. However, to the extent that the method or process does not relyon the particular order of steps set forth herein, the method or processshould not be limited to the particular sequence of steps described.Other sequences of steps may be possible. Therefore, the particularorder of the steps disclosed herein should not be construed aslimitations of the present disclosure. In addition, disclosure directedto a method and/or process should not be limited to the performance oftheir steps in the order written. Such sequences may be varied and stillremain within the scope of the present disclosure.

1. A method, comprising: introducing at least part of a systemcomprising a balloon configured for inflation into a luminal organ sothat the balloon is adjacent to a valve annulus or opening; introducinga valve device within the valve annulus or opening, adjacent theballoon; moving the valve device within the valve annulus or opening;operating the system to obtain measurements of the balloon over timeduring the step of moving the valve device within the valve annulus oropening; and generating a real-time measurement profile of themeasurements over time.
 2. The method of claim 1, wherein the method isperformed to assess left ventricular outflow tract (LVOT) reductionduring a valve replacement procedure.
 3. The method of claim 1, whereinthe measurements are size measurements, and wherein the method isperformed to produce accurate mitral annular sizing measurements.
 4. Themethod of claim 1, further comprising the step of: obtaining at leastone initial measurement of the balloon when adjacent to the valveannulus or opening prior to the step of introducing the valve devicewithin the valve annulus or opening, the at least one initialmeasurement selected from the group consisting of an initial sizingmeasurement and an initial pressure measurement.
 5. The method of claim1, wherein the real-time measurement profile can indicate externalpinching of the balloon from the valve device when the real-timemeasurement profile indicates a decrease in size of the balloon.
 6. Themethod of claim 1, wherein an axis of fluid flow through the valveannulus or opening is defined as an optimal axis of flow, and whereinthe step of moving the valve device is performed to align the devicealong and consistent with a perpendicular axis that is perpendicular tothe axis of fluid flow, wherein the perpendicular axis corresponds to anaxis of the valve annulus or opening.
 7. The method of claim 6, whereinwhen the step of moving the valve device causes an increase in pressurewithin the balloon, which is indicative of improper alignment of thevalve device within the valve annulus or opening.
 8. The method of claim6, wherein the measurements are pressure measurements, wherein when thestep of moving the valve devices causes a change in pressure within theballoon, and wherein a relative lowest pressure within the balloon isindicative of proper alignment of the valve device within the valveannulus or opening.
 9. The method of claim 1, wherein the real-timesizing profile corresponds to a degree of left ventricular outflow tract(LVOT) obstruction over time.
 10. The method of claim 1, wherein themeasurements comprise size measurements, wherein the system furthercomprises at least two detection electrodes positioned in between twoexcitation electrodes, wherein excitation of the two excitationelectrodes permits impedance measurements to be obtained within theballoon, and wherein the impedance measurements correspond to the sizemeasurements.
 11. The method of claim 7, wherein the increase inpressure is determined using a pressure sensor or pressure transducerpositioned within the balloon.
 12. The method of claim 1, wherein themeasurements comprise pressure measurements, wherein the real-timemeasurement profile comprises a real-time pressure measurement profile,wherein the system further comprises a pressure sensor or pressuretransducer positioned within the balloon, and wherein the step ofgenerating the real-time measurement profile is performed to generatethe real-time pressure measurement profile.
 13. The method of claim 1,wherein the system further comprises at least two detection electrodespositioned in between two excitation electrodes, wherein the system doesnot comprise a pressure sensor or pressure transducer, and wherein thestep of operating the system is performed to obtain the measurementscorresponding to size measurements of the balloon over time.
 14. Themethod of claim 1, wherein the system further comprises a pressuresensor or pressure transducer positioned within the balloon, wherein thesystem does not comprise any excitation electrodes or any detectionelectrodes, and wherein the step of operating the system is performed toobtain the measurements corresponding to pressure measurements withinthe balloon over time.
 15. The method of claim 1, wherein the systemfurther comprises at least two detection electrodes positioned inbetween two excitation electrodes, wherein the system further comprisesa pressure sensor or pressure transducer positioned within the balloon,and wherein the step of operating the system is performed to obtain themeasurements corresponding to size measurements of the balloon over timeand pressure measurements within the balloon over time.
 16. A method,comprising: performing a valve replacement procedure using a valvedevice positioned within a valve annulus or opening of a luminal organwhile a system comprising a balloon configured for inflation is at leastpartially introduced into a luminal organ so that the balloon isadjacent to a valve annulus or opening.
 17. The method of claim 16,further comprising: operating the system to obtain measurements of theballoon over time during the valve replacement procedure; and generatinga real-time measurement profile of the measurements over time.